Effects of albumin and/or furosemide therapy on pulmonary edema induced by hydrochloric acid aspiration in rabbits

Aspiration of hydrochloric acid in rabbits resulted in an increased P(A-a)O2 together with increases in both lung water volume and lung extravascular albumin. This finding suggests lung damage following acid aspiration is related to changes in capillary permeability, with pulmonary edema resulting from the movement of albumin and water into the interstitial space. Therapy with albumin and furosemide together reduced the lung water and albumin accumulation and decreased P(A-a)O2. Treatment with albumin or furosemide alone was ineffective. Caution should be exercised in administering albumin alone for therapy of pulmonary edema when plasma protein is not clearly decreased, or when increased pulmonary capillary permeability is suspected.     

Oxygen intake and walking speed before and after total hip replacement

The objective of the study was to evaluate the walking ability and the energy cost of walking in patients before and after total hip replacement. The oxygen intake and the maximum walking speed were measured immediately before and 6 months after operation in 25 patients. Although the oxygen intake did not change significantly in most patients it was decreased in those patients who before surgery had had the worst walking capacity. The average maximum walking speed almost doubled in the 25 patients.     

Theory of non-equilibrium phenomena in an MIS device under linear voltage ramp bias

A theoretical investigation into the non-equilibrium characteristics displayed by a metal-insulator-semiconductor (MIS) device when subjected to a linear voltage ramp is presented. Unlike previous theoretical analyses a time varying bulk trap generation rate is considered. It is shown that the current-voltage characteristics obtained by including this time dependence are the same as those obtained by assuming the bulk traps generate instantly at their steady-state value. Two different starting conditions are considered, namely, accumulation or depletion and strong inversion. The problem associated with commencing the sweep in accumulation or depletion when the concern is only with bulk properties is one of interface trap emission and generation and the effect these may have on the resulting I–V characteristic. This is overcome by initially biasing the device into strong inversion. For this condition bulk trap generation actually takes place right up to the semiconductor surface even though those traps near the surface have an initial occupancy of zero.     

A G protein gamma subunit-like domain shared between RGS11 and other RGS proteins specifies binding to Gbeta5 subunits

Regulators of G protein signaling (RGS) proteins act as GTPase-activating proteins (GAPs) toward the alpha subunits of heterotrimeric, signal-transducing G proteins. RGS11 contains a G protein gamma subunit-like (GGL) domain between its Dishevelled/Egl-10/Pleckstrin and RGS domains. GGL domains are also found in RGS6, RGS7, RGS9, and the Caenorhabditis elegans protein EGL-10. Coexpression of RGS11 with different Gbeta subunits reveals specific interaction between RGS11 and Gbeta5. The expression of mRNA for RGS11 and Gbeta5 in human tissues overlaps. The Gbeta5/RGS11 heterodimer acts as a GAP on Galphao, apparently selectively. RGS proteins that contain GGL domains appear to act as GAPs for Galpha proteins and form complexes with specific Gbeta subunits, adding to the combinatorial complexity of G protein-mediated signaling pathways.     

Identification of a gene that causes primary open angle glaucoma

Glaucoma is a major cause of blindness and is characterized by progressive degeneration of the optic nerve and is usually associated with elevated intraocular pressure. Analyses of sequence tagged site (STS) content and haplotype sharing between families affected with chromosome 1q-linked open angle glaucoma (GLC1A) were used to prioritize candidate genes for mutation screening. A gene encoding a trabecular meshwork protein (TIGR) mapped to the narrowest disease interval by STS content and radiation hybrid mapping. Thirteen glaucoma patients were found to have one of three mutations in this gene (3.9 percent of the population studied). One of these mutations was also found in a control individual (0.2 percent). Identification of these mutations will aid in early diagnosis, which is essential for optimal application of existing therapies.     

Histopathologic spectrum of vaginal adenosis and related changes in stilbestrol-exposed females

A total of 98 colposcopically directed biopsies were obtained from the vagina, cervix, and cervicovaginal ridge (hood) of 80 young women believed to have had intrauterine exposure to stilbestrol (DES). Specific investigation of the patient's medical records corroborated the history of maternal stilbestrol administration in 36 patients (45%), while in the remainder the drug history was regarded as presumptive since medical records were unavailable for review. The findings did not differ significantly in those biopsies taken from patients with confirmed or presumptive drug histories. Histologic evidence of vaginal adenosis was detected in vaginal biopsies from 43 patients. In 30 cases (70%) benign Müllerian-type glandular epithelium was in the superficial vaginal wall, residing on the mucosal surface and/or in the lamina propria. The glandular epithelium predominantly was of endocervical type, but in six instances it resembled endometrial or fallopian tubal epithelium. The glands were accompanied by varying degrees of squamous metaplasia in 22 cases. When extensive the metaplasia produced transformation zones similar to those seen in the normal cervix. Vaginal biopsies of adenosis from the other 13 patients (30%) revealed squamous metaplasia without demonstrable glands due to complete transformation of all antecedent glandular epithelium by squamous metaplasia. Our studies indicate that squamous metaplasia is a component of major importance in the natural history of adenosis and that the concept of adenosis should be broadened to include those examples comprised exclusively of metaplastic epithelium. In such examples metaplasia is identified by the immaturity and poor glycogenation of the squamous cells and their accompanying squamous pegs which often contain residual gland openings or squamous "eddies." Similar findings were present in biopsies of seven cervicovaginal ridges and in cervical biopsies from 37 patients, except for the absence of endometrial or tubal type glands in the latter site. Although no adenocarcinomas were detected, six patients had squamous dysplasia of the vagina and/or cervix. In no case were premalignant or dysplastic changes of glandular cells found. Our findings support the thesis that stilbestrol-associated adenosis represents anomalous embryologic localization of the original squamocolumnar junction in the vagina rather than in the cervix. It is closely related to so-called cervical "erosions." The development of squamous metaplasia accounts for modifications in the clinical and histologic appearances by producing transformation zones which then may be subject to the same oncogenic stimuli for squamous neoplasia as are their counterparts in the cervix.     

Transthoracic defibrillation of swine with monophasic and biphasic waveforms

BACKGROUND: Biphasic waveforms have had a favorable impact on internal defibrillation but have seen minimal use in transthoracic defibrillation systems. The purpose of this study was to compare monophasic and biphasic waveforms for transthoracic defibrillation in swine. METHODS AND RESULTS: Three interrelated studies were performed in 19 swine to establish the relative transthoracic defibrillation efficacy of biphasic shock waveforms. In study 1, we measured voltage (V50) and energy (E50) strength-duration curves for monophasic and biphasic truncated exponential waveforms. We then independently examined the effects of phase duration and tilt on biphasic waveform defibrillation with a total waveform duration from study 1 that provided the minimum V50 (study 2) and the minimum E50 (study 3). At each pulse duration tested in study 1, biphasic waveforms defibrillated with significantly less voltage and energy than monophasic waveforms. At a duration of 12 ms, there was a voltage minimum for biphasic waveform defibrillation. At this duration, V50 was 1378 +/- 505 V for the biphasic waveform compared with 2185 +/- 361 V for the monophasic waveform, P = .01. For both monophasic and biphasic waveforms, E50 increased with pulse duration. With a total pulse duration of 12 ms, E50 was 169 +/- 101 J for the biphasic waveform compared with 414 +/- 114 J for the monophasic waveform, P = .003. In study 2, optimization of phase duration and total tilt reduced the defibrillation requirements of the 12-ms "minimum voltage" biphasic waveform to 1284 +/- 187 V and 129 +/- 36 J. In study 3, the 8-ms "minimum energy" biphasic waveform had an E50 of 115 +/- 35 J that was 11% less than the 12-ms biphasic waveform, P = .11; however, voltage requirements of 1476 +/- 239 V were 15% higher, P = .005. CONCLUSIONS: This study demonstrates the superiority of truncated biphasic waveforms over truncated monophasic waveforms for transthoracic defibrillation of swine. Biphasic waveforms should prove as advantageous at reducing voltage and energy requirements for transthoracic defibrillation as they have for internal defibrillation.     

Immunoelectron microscopic localization of plasminogen activator inhibitor type 1 (PAI-1) in smooth muscle cells from morphologically normal and atherosclerotic human arteries

Vascular wall fibrinolytic system proteins are believed to play a pivotal role in atherogenesis. Tissue-type plasminogen activator (t-PA) and urokinase plasminogen activator (u-PA) influence persistence of luminal thrombi and proteolysis of extracellular matrix, respectively. The major physiologic inhibitor of t-PA and u-PA is plasminogen activator inhibitor type 1 (PAI-1). All three of these fibrinolytic system proteins have been detected in vascular endothelial cells, smooth muscle cells, and macrophages by light microscopic immunohistochemistry. This study was undertaken to delineate, by immunoelectron microscopy, the loci of PAI-1 in smooth muscle cells from intact morphologically normal and atherosclerotic human arteries as well as in isolated and cultured smooth muscle cells from arteries. In intact vessels, PAI-1 immunoreactivity was associated with contractile filaments in cells in both normal and atherosclerotic tissues. Lipid-laden smooth muscle cells in atherosclerotic vessels were mainly of the synthetic phenotype and displayed lesser amounts of PAI-1 associated with rough endoplasmic reticulum and contractile filaments. Isolated smooth muscle cells exhibited either a contractile or synthetic phenotype. In the cells with a contractile phenotype, PAI-1 was associated with the contractile elements, whereas in the cells with a synthetic phenotype, the PAI-1 was associated predominantly with elements of the endoplasmic reticulum. Because PAI-1 is associated predominantly with contractile filaments in smooth muscle cells, the net amount of immunodetectable PAI-1 appears to be greater in contractile compared with synthetic phenotype cells.