Hydatid cyst of the interventricular septum in a 3.5-year-old child

An asymptomatic cardiac cyst located in the interventricular septum was diagnosed in a 3.5-year-old child by echocardiographic findings. Surgical ablation was done and histopathologic analysis confirmed a hydatid cyst. The patient was discharged without symptoms.     

Molecular mapping with functional antibodies localizes critical sites on the human IL receptor common gamma (gamma c) chain

The IL receptor common gamma (gamma c) chain is required for the formation of high affinity cytokine receptor complexes for IL-2, IL-4, IL-7, IL-9, and IL-15, and for signals regulating cell survival, growth, and differentiation. Our current understanding of how gamma c chain associates with multiple ligands and receptor subunits is drawn largely from its structural homology to the human growth hormone (hGH) receptor and known structure of the hGH/hGH receptor complex. These receptors share distinct features in their extracellular portions and are believed to function by a mechanism of ligand-induced association of receptor subunits. Here, we report the first directed mutational analysis of the human gamma c chain by alanine scanning conducted across seven regions likely to contain residues required for intermolecular contact. Functionally distinct, neutralizing anti-gamma c mAbs were employed to define critical residues. One particular mAb, CP.B8, unique in its ability to inhibit IL-2-, IL-4-, IL-7-, and IL-15-induced proliferation and high affinity cytokine binding of normal T cells as an intact mAb and as a Fab fragment, localized critical residues to four noncontinuous stretches, namely residues in loops AB and EF of domain 1, in the interdomain segment, and in loop FG of domain 2. Notably, these residues form a contiguous patch on the gamma c chain surface in a three-dimensional structural model. These results provide functional evidence for the location of contact points on gamma c chain required for its association with multiple ligands.     

Characterization of hydrogen bonding in the complex of adenosine deaminase with a transition state analogue: a Raman spectroscopic study

The Raman spectra of purine ribonucleoside as well as a stable model compound (1-methoxyl-1,6-dihydropurine ribonucleoside), free in solution and bound into its complex with adenosine deaminase (ADA), have been studied by Raman difference spectroscopy. Using purine riboside analogues labeled with 15N1 or 13C6 and the theoretical frequency normal-mode analyses of these molecules using ab initio quantum mechanic methods, we have positively identified many of the Raman bands in the enzyme-bound inhibitor. The spectrum of the enzyme-bound inhibitor is consistent with the enzyme-catalyzed hydration of the purine base to yield 1-hydroxyl-1,6-dihydropurine ribonucleoside, as suggested earlier by X-ray crystallographic studies. In addition, the Raman data and subsequent vibrational analyses show that the binding-induced Raman spectral changes of the inhibitor can be modeled by the formation of a strong hydrogen bond to its N1-H bond. This hydrogen bond, apparently between the N1-H of the inhibitor and the Odelta1 of Glu217 in ADA, causes a substantial N1-H bending frequency increase of about 50-100 cm-1 compared to its solution value, and this results in an estimated enthalpy of the hydrogen bond of 4-10 kcal/mol. The relationship of transition state stabilization in the catalytic strategy of this efficient enzyme to such a bonding pattern is discussed.     

Structure and practice of institutional review boards in the United States

OBJECTIVE: The institutional review board (IRB) is a critical element in the protection of patients' and subjects' rights with regard to their participation in research protocols. The purpose of this study was to describe the structure and current practices of IRBs in the United States. METHODS: A self-administered questionnaire was mailed to the IRB chair of each U.S. hospital with a capacity of at least 400 beds (n = 907). The survey contained 21 questions outlining committee size and structure, review of research proposals, and policies concerning scientific misconduct. Chairs also were asked what advice they would offer a young investigator preparing a proposal for submission. RESULTS: A total of 488 surveys (54%) were returned; 447 of the responding institutions had an IRB committee. Committees had an average of 14 members, representing 27 medical specialties. Orthopedics had the least IRB representation (10% of committees), followed by emergency medicine (12%) and ophthalmology (15%). The majority of research proposals go through 5 specific steps once submitted for review. Common reasons for proposal rejection were improperly designed consent form (54%), poor study design (44%), unacceptable risk to subjects (34%), ethical or legal reasons (24%), and scientific merit (14%). When a research proposal is rejected, 86% of the responding IRBs assist the investigator in making appropriate revisions. Although a number of IRBs (17%) have dealt with scientific misconduct allegations, only 58% have a written policy regarding research integrity. CONCLUSION: Despite variations in committee structure and representation, IRBs have similar procedures for governing research. Investigators should be familiar with these procedures and are encouraged to discuss their proposal with an IRB representative prior to formal review.     

Pseudomonas keratitis. The role of an uncharacterized exoprotein, protease IV, in corneal virulence

PURPOSE: The role of exoproteins in the pathogenesis of Pseudomonas aeruginosa keratitis was investigated in three animal models by assessing the relationship between corneal virulence and the activities of exotoxin A, elastase, alkaline protease, and an uncharacterized protease, protease IV. METHODS: The four Pseudomonal strains tested included a prototype strain (ATCC 27853) producing exotoxin A, elastase, and alkaline protease; a parent strain (PA103) producing only exotoxin A and protease IV; a mutant (PA103-29) producing only protease IV; and a mutant (PA103-AP1) producing exotoxin A and having only approximately 5% of the protease IV activity of its parent. Corneal virulence was evaluated in the mouse scratch, rabbit scratch, and rabbit intrastromal models in terms of clinical signs (slit lamp examination, slit lamp examination), and viable bacteria. RESULTS: Protease IV, the only protease produced by PA103 and PA103-29, was found to produce a unique band on zymograms (120 kDa) and to react distinctively with a synthetic substrate. Evidence for the role of protease IV in corneal virulence included two findings: PA103-29,which produced protease IV but not the other exoproteins, caused infections that were as severe as those caused by the prototype strain (ATCC 27853) in all three models (P>0.24); and PA103-AP1, the strain deficient in 95% of the parent protease IV activity, mediated infections characterized by slit lamp examination scores significantly lower than those of infections caused by the parent (PA103) or the prototype strain (ATCC 27853) in the rabbit and mouse scratch models (P<0.02). CONCLUSIONS: Protease IV was found to be a novel Pseudomonas protease contributing to corneal virulence in rabbits and mice when infections were initiated at the corneal surface. Furthermore, production of protease IV in low quantities was sufficient for virulence when the topical stages of keratitis were bypassed by an intrastromal injection of Pseudomonas.     

Effects of cold and warm blood cardioplegia assessed by myocardial pH and release of metabolic markers

The optimal temperature of blood cardioplegia remains controversial. Interstitial myocardial pH was monitored online with a probe that was inserted in the anterior wall of the left ventricle. Venous pH, lactate production, and creatine kinase and troponin T release were measured in coronary sinus blood obtained in 14 dogs after ischemic arrest periods of 5, 10, 20, and 40 minutes with warm (n = 7; mean myocardial temperature, 35 degrees +/- 2 degrees C) and cold (n = 7; mean myocardial temperature, 12 degrees +/- 1 degree C) blood cardioplegic protection. Blood cardioplegic solution was delivered at a rate of 100 mL/min during the 10 minutes between each ischemic arrest. The interstitial myocardial pH decreased significantly (p < 0.05) from 7.1 +/- 0.3 to 6.53 +/- 0.3 after ischemia in animals perfused with warm blood cardioplegia and from 7.04 +/- 0.3 to 6.64 +/- 0.1 in those receiving cold blood cardioplegic protection; however, the difference between the groups was not significant (p > 0.05). Lactate production and creatine kinase and troponin T release increased significantly after ischemia, but there was no difference in the changes between the warm and cold blood cardioplegia groups. In conclusion, ischemia caused significant changes in all variables measured, and these changes were directly proportional to the duration of ischemia. However, there was no significant difference (p > 0.05) in the myocardial metabolic changes between the warm and cold blood cardioplegia groups in terms of the duration of ischemic arrest studied.(ABSTRACT TRUNCATED AT 250 WORDS)     

Word completion in chronic pain: evidence for schematic representation of pain?

Schematic representation of pain information was investigated in chronic pain patients, health professionals, and nonpatient controls. Under the guise of an English-language experiment, Ss were presented with 12 word stems to be completed with the first 2 English words that came to mind. Four of the stems could be completed with sensory pain words, 4 with effective, and 4 with words associated with pain or illness. All could be completed with at least 3 other nonpain words of equal or greater frequency. Results indicate that chronic pain Ss produced significantly more pain-related completions than control Ss and that in all 3 groups the types of pain words produced were related to the extent of personal experience of pain. The theoretical implications of these findings are discussed in relation to the organization of schema, implicit memory, and the activation of mental representations of pain (schema).     

Quantification of device adherent, circulating, and organ pool of thrombin and fibrinogen after cardiopulmonary bypass in a pig model

The pool of thrombin and fibrinogen in circulation, in organs, and on cardiopulmonary bypass devices was quantified during and after cardiopulmonary bypass in four groups of 24 Yorkshire pigs (weight, 30-35 kg); two groups of 10 unoperated pigs were used as controls. Thrombin-alpha and fibrinogen were iodinated with 125iodide using an iodogen transfer technique; 250-300 microCi of these tracers were injected intravenously 1 hr before cardiopulmonary bypass. All pigs were systematically heparinized (activated clotting time > 400 sec); cardiopulmonary bypass was performed at 2.5-3.5 L/min at 28 degrees C using a centrifugal pump, oxygenator (Bentley Univox 1.8 m2; Bentley Inc., Irvine, CA), arterial filter (0.25 m2), and cardiotomy reservoir (BMR 3500) for 90 min, followed by a 90 min reperfusion and 180 min of cardiopulmonary bypass. Iodinated thrombin-alpha and fibrinogen in intact organs and samples of blood, organs, tissues, and oxygenator-arterial filter-cardiotomy reservoir were quantified with an ion chamber and a gamma counter, respectively. The percent of injected iodinated thrombin-alpha and fibrinogen dose (mean +/- SD) in organs and cardiopulmonary bypass devices of all groups of cardiopulmonary bypass pigs was calculated. Thrombin generated at the small area of surgical wounds (0.016-0.038 m2), and fibrin deposited on surfaces of cardiopulmonary bypass devices (2.59 m2), initiate and propagate thrombus formation and embolization. The protein level reached saturation values on all cardiopulmonary bypass devices at 180 min. High levels of thrombin and fibrinogen-fibrin circulate in blood and organs, and are adsorbed on cardiopulmonary bypass devices; this large blood pool of pro-coagulants in the cardiac cradle, tissues, and perfused organs may account for thrombi and emboli during and after cardiopulmonary bypass.     

Portal hypotensive effects of DL-028 and prazosin on portal hypertensive rats

The portal hypotensive effects of prazosin and DL-028 (chem- ical name: 3-[[4-(2-methoxyphenyl)piperazin-1-yl]methyl]- 2, 3-dihydroimidazo[1,2-c]quinazolin-5(6H)-one(27b)), a synthetic alpha1-adrenoceptor antagonist, were assessed in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation in Sprague-Dawley rats. Two weeks after ligation, when the hyperdynamic state was stabilized the rats were anesthetized after an overnight fast and cannulated for measuring mean arterial pressure (MAP), portal venous pressure (PVP), cardiac index (CI) and heart rate (HR). Both DL-028 and prazosin (1, 3.3 and 10 microgram/kg) induced dose-dependent decreases of PVP and MAP after intravenous infusion, with effects lasting for longer than 30 min. The maximum percentage reduction of PVP after DL-028 was 10, 10 and 15%, respectively, for the dosages given (1, 3.3 and 10 microgram/kg), and 5, 12 and 25%, respectively, after prazosin. CI was not changed by either drug. HR was not changed by either drug except DL-028 at 10.0 microgram/kg with a bradycardiac effect. Our results showed that both DL-028 and prazosin reduced PVP in portal hypertensive rats.