Anticoagulant activity in cell-free peritoneal fluid of an experimental pancreatic ascites tumor.

The ascitic form of a chemically-induced pancreatic ductal adenocarcinoma in the Syrian golden hamster was very bloody and indistinguishable from blood macroscopically. Unlike blood, the bloody fluid remained unclotted at room temperature. To explore the possibility of presence of anticoagulants, we mixed 40% cell-free fluid with 60% normal human plasma and tested the clottability of the mixture with standard techniques. Plasma containing the fluid showed markedly prolonged activated partial thromboplastin time (APTT), thrombin time (TT) and recalcification time (RCT), and normal prothrombin time (PT) and reptilase time (RT). Comparing the prolongation of APTT of samples containing the fluid to those containing a commercial heparin, the fluid contained an anticoagulant activity equivalent to 0.436 +/- 0.03 unit heparin per ml (mean +/- SEM, n = 14). In addition to prolonging the APTT, TT and RCT, the fluid also inhibited the clotting and amidolytic activities of thrombin. "Heparsorb" had nearly completely neutralized the anticoagulant activity in fluid samples, while protamine sulfate was only partially effective. Incubation of fluid with pronase or phospholipase did not affect its anticoagulant activity; incubation with heparinase had only a minimal effect. Electrophoresis of an alkali digested fluid on cellulose acetate revealed the presence of heparan sulfate. The native ascitic fluid also contained other hemostatic components including platelets, fibrinogen and antithrombin III, but their concentrations were much lower than in blood. Apparently, heparan sulfate in the neoplastic effusion is largely responsible for the bloody ascites tumor remaining unclotted.

Propafenone for the treatment of refractory complex ventricular ectopic activity.

The results of therapy with propafenone were evaluated in 45 patients with complex ventricular ectopic activity that had been refractory to a mean of 3.8 antiarrhythmic drugs. The cardiac diagnoses were ischemic heart disease (in 16 patients), cardiomyopathy (in 7), mitral valve prolapse (in 7), mitral valve prolapse (in 7), idiopathic ventricular ectopic beats (in 6), valvular heart disease (in 5), and hypertension (in 4). The frequency of ventricular ectopic beats was established after therapy with antiarrhythmic agents had been discontinued. Patients then received propafenone during a dose-ranging protocol. An effective response was defined as a reduction in total ventricular ectopic beats of 80% or more. During dose ranging, therapy failed in four patients because of side effects, in eight because of a reduction in ventricular ectopic beats of less than 80%, and in three because of an aggravation of the arrhythmia. Thirty patients had a reduction in total ventricular ectopic beats of 80% or more. During a mean follow-up of 12.4 months, therapy failed in 1 patient because of sustained ventricular tachycardia and in 7 because of intolerable side effects; 22 patients continued to receive propafenone. PR and QRS intervals were significantly prolonged (P = 0.001), but the corrected QT interval and the heart rate were unchanged. The mean trough plasma level of propafenone associated with an effective response was 756 ng/ml, and that associated with intolerable side effects was 920 ng/ml. Thus, in patients with refractory complex ventricular ectopic beats, propafenone was effective and well tolerated initially in 67% of patients and during long-term administration in 49%, and toxicity was minor in most patients.

The Ginzburg-Landau approach to oscillatory media.

Close to a supercritical Hopf bifurcation, oscillatory media may be described, by the complex Ginzburg-Landau equation. The most important spatiotemporal behaviors associated with this dynamics are reviewed here. It is shown, on a few concrete examples, how real chemical oscillators may be described by this equation, and how its coefficients may be obtained from the experimental data. Furthermore, the effect of natural forcings, induced by the experimental realization of chemical oscillators in batch reactors, may also be studied in the framework of complex Ginzburg-Landau equations and its associated phase dynamics. We show, in particular, how such forcings may locally transform oscillatory media into excitable ones and trigger the formation of complex spatiotemporal patterns.

Cardiopulmonary effects of positive end-expiratory pressure in anesthetized horses.

The cardiopulmonary effects of 0, 5, 10, and 15 cm of H2O positive end-expiratory pressures (PEEP) were determined in anesthetized, spontaneously breathing horses, using a 4 by 4 Latin-square design with one repetition. Cardiac output, alveolar-arterial oxygen tension difference, alveolar ventilation, dead space/tidal volume ratio, and carbon dioxide elimination were not significantly altered by the procedure. As PEEP was increased, alveolar and arterial oxygen tensions, respiratory exchange ratio, and pH decreased, whereas arterial carbon dioxide tension and oxygen consumption increased. These results indicate PEEP is contraindicated in laterally recumbent spontaneously ventilating anesthetized horses breathing air, because it causes alveolar hypoventilation and does not improve pulmonary gas exchange.

Pathophysiology of airway obstruction in horses: a review.

Obstruction of the upper and lower airways is common in horses. In the upper airway, paresis of abductor muscles of the nares and larynx allows inspiratory collapse of soft tissues, which is accentuated by factors increasing upper airway resistance and by high inspiratory flow rates. Intrapulmonary airway obstruction occurs due to accumulation of secretions, release of chemical mediators in response to a variety of stimuli, and parasympathetic stimulation of airways. Obstruction of large airways increases the work of breathing, whereas obstruction of small airways may cause no measurable increase in resistance but does cause uneven distribution of ventilation and hypoxemia, especially during exercise. Poor collateral ventilation accentuates gas exchange problems in the horse with airway obstruction and may be a factor causing intrapulmonary hemorrhage during racing.

Universal hearing screening in the NICU: the Loma Linda University Children's Hospital experience.

The most common birth defect in the U.S. today is hearing loss, ranging from mild to profound. Even mild hearing impairment seriously affects language, speech, and cognitive development. Early identification and intervention lead to improved communication skills, which positively impact psychosocial, educational, and vocational development. Loma Linda University Children's Hospital NICU has implemented a program consistent with the Joint Committee on Infant Hearing's 1994 position statement, which advocates universal detection of infants with hearing loss, and with the National Institutes of Health 1993 position statement on early identification of hearing impairment in infants and young children, which recommends screening all infants admitted to NICUs for hearing loss prior to discharge. This article discusses the process of change required to meet these goals and outlines areas for further evaluation and change.

Collateral flow resistance and time constants in dog and horse lungs.

We studied collateral flow resistance in exsanguinated, excised lower lobes and accessory lobes of dog and horse lungs, respectively. A double lumen catheter obstructed a peripheral airway isolating a segment of the lobe. Oxygen flowed into the segment via a rotameter which measured flow (Vcoll) while the inner catheter recorded segment pressure (Ps). Gas delivered into the segment flowed out via collateral channels. Collateral flow resistance was calculated as (Ps - PL)/Vcoll, where PL = static transpulmonary pressure. Rcoll at PL = 20, 10, and 5 cm H2O averaged 0.24, 1.25, and 2.65 cmH2O.ml-1.s, respectively, in the dog, and 4.53, 6.00, and 12.62 cmH2O.ml-1.s in the horse. At a given PL, Rcoll measured during inflation. At constant PL, Rcoll increased with time at PL = 5 and 10 cmH2O, but was not time dependent at PL = 20 cmH2O. At constant PL, Rcoll increased at Vcoll increased. We conclude Rcoll is greater in horses than in dogs and is a function of PL, Ps - PL, and lung volume history in both species.

Postural effects on lung volumes and asynchronous ventilation in anesthetized horses.

Quasi-static pressure-volume curves and single-breath nitrogen washouts were performed simultaneously on eight anesthetized horses (average body wt = 485 kg) in left lateral, right lateral, prone, and supine postures (sequence randomized). The shift from prone to lateral or supine posture decreased expiratory reserve volume (ERV), vital capacity (VC), residual volume (RV), functional residual capacity (FRC), and total lung capacity (TLC); RV and FRC expressed as %TLC were unchanged, suggesting that in the lateral and supine postures a significant portion of the lung volume was not recruited by VC maneuvers. Phase III slope increased from 0.13 %N2/l in prone horses to 0.34 %N2/l in the lateral and supine positions. The onset of phase IV was not significantly different from FRC in the prone or laterally recombent animal, but exceeded FRC in the supine horse. The sequence of body positions had no effect on any of our results indicating that all changes in lung volumes and regional asynchronous ventilation c;n be reversed by placing the horse in the prone posture. The reduction in lung volume and increased asynchronous ventilation in the lateral and supine horse suggests that impaired gas exchange in anesthetized horses is predominantly related to posture, and not general anesthesia.

The pro region required for folding of carboxypeptidase Y is a partially folded domain with little regular structural core.

The pro region of carboxypeptidase Y (CPY) from yeast is necessary for the correct folding of the enzyme [Winther, J. R., & Sørensen P. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 9330-9334]. Using fluorescence, circular dichroism, and heteronuclear NMR analyses, it is demonstrated that the isolated pro region is a partially folded protein domain under the conditions where it is functional. It is characterized by a relatively high content of secondary structural elements but a very low content of defined tertiary structure. Although these characteristics are reminiscent of the compact denatured states that have been identified as intermediates in protein folding ("molten globules"), the pro region exhibits only very weak binding of the hydrophobic probe 1-anilino-8-naphthalenesulfonate, and it is resistant toward complete thermal unfolding. Altogether the data indicate an extremely flexible structure that has little regular structural core. It is proposed that the feature of a partially folded domain per se is important for the function of the pro region of CPY as a "co-translational chaperone".

Radioprotectant Activity of 5-Diethylsulfonamoylsalicylatocopper(II) in Gamma Irradiated Mice.

Survival and changes in mean body mass of whole-body irradiated mice were determined to examine the radioprotectant activity of 5-diethylsulfonamoylsalicylatocopper(II) [Cu(II) (5-DESS)]. One of four groups of 25 female C57BL/6 mice were treated subcutaneously (sc)with 0, 10, 20, 40, 60, 80, 100, or 120 mumol Cu(II)(5- DESS)/kg of body mass 3 hours before exposure to 8.0 Gy, gamma irradiation. In this paradigm, doses of Cu(II)(5- DESS) increased survival up to 92% above vehicle-treated control mice (P = 0.008). Mean body mass determinations revealed that mice treated with 80 to 120 mumol Cu(II)(5-DESS)/kg of body mass exhibited a smaller decrease in body mass than other complex-treated groups. These results support the hypothesis that Cu(II)(5-DESS) is an effective radioprotectant.