Diuretics: role of sodium balance

Diuretics are commonly prescribed for a wide variety of clinical problems, including hypertension, extracellular volume excess, and disorders of calcium metabolism. Although natriuresis with altered sodium balance is not always the therapeutic goal, this feature of the diuretics is essential for optimal results, irrespective of the clinical problem.     

Structural interaction of natural and synthetic inhibitors with the venom metalloproteinase, atrolysin C (form d)

The structure of the metalloproteinase and hemorrhagic toxin atrolysin C form d (EC 3.4.24.42), from the venom of the western diamondback rattlesnake Crotalus atrox, has been determined to atomic resolution by x-ray crystallographic methods. This study illuminates the nature of inhibitor binding with natural (< Glu-Asn-Trp, where < Glu is pyroglutamic acid) and synthetic (SCH 47890) ligands. The primary specificity pocket is exceptionally deep; the nature of inhibitor and productive substrate binding is discussed. Insights gained from the study of these complexes facilitate the design of potential drugs to treat diseases where matrix metalloproteinases have been implicated, e.g., arthritis and tumor metastasis.     

Temperament as a predictor of behavior during initial dental examination in children

Temperament refers to children's behavioral style, or the manner in which they interact with their environment. Temperament has been quantified into nine temperament categories and five temperament constellations by Thomas and Chess. Temperament categories and constellations of children can be measured using one of several parental questionnaires, each of which focuses on age-appropriate behavior. For this study the Behavioral Style Questionnaire (BSQ) was administered to the parents of 50 healthy children (mean age 48.8 months) receiving initial dental examinations. The examinations were videotaped and The Ohio State Behavior Rating Scale (OSUBRS) was used to rate each child's behavior into one of four behavioral categories: 1) quiet; 2) crying only; 3) disruptive movement only; and 4) crying and disruptive movement. For data analysis the percentage duration of each behavioral category was calculated. Using one-way ANOVA, significant differences between constellations were found for quiet (P = 0.03) and combination behavior (P = 0.03). Using a stepwise linear regression, the temperament category of approach/withdrawal was found to predict the percentage of quiet (multiple R = 0.42357, R2 = 0.17941, and P = 0.002), crying (multiple R = 0.42124, R2 = 0.17744, and P = 0.002), and combination behaviors (multiple R = 0.30008, R2 = 0.09005, and P = 0.03). Additionally, significant regressions were found with temperament categories predicting behavioral categories depending on the child's age. The results of this pilot study suggest that the BSQ temperament constellations and categories appear to be modest predictors of a child's specific behaviors in the dental environment. Knowledge of a child's temperament may prepare the clinician to predict patient behaviors in the dental environment.     

Prognostic factors in the acute lymphoid and myeloid leukemias of infants

The age boundaries and prognostic factors that define the infant leukemias are still controversial. We therefore analyzed event-free survival according to age group in 96 children treated for acute lymphoblastic leukemia (ALL) and 51 treated for acute myeloid leukemia (AML) before the age of 2 years. The study population was registered in consecutive institutional trials of multiagent chemotherapy conducted between 1980 and 1994. Among infants with ALL, event-free survival was significantly poorer in the 0- to 6-month-old group than in patients treated between 6 and 12 months of age (P = 0.03), whose outcome was in turn inferior to that in the 12- to 18-month and 18- to 24-month age groups (P = 0.013). Leukemic cells from ALL patients younger than 12 months had a significantly higher frequency of 11q23/MLL abnormalities, as well as better growth in stromal cell culture, compared to lymphoblasts from the older groups (P < 0.01). The only independent predictor of adverse prognosis among infants diagnosed with ALL before age 12 months was the presence of an 11q23/MLL rearrangement (P = 0.03). These findings contrast sharply with results for the AML cohort, whose event-free survival did not vary significantly by age group (P = 0.58). Male sex (P = 0.01) and leukocyte count > or = 50 x 10(9/l) (P = 0.04), but not 11q23 abnormalities, were independently associated with a poorer outcome for children with AML younger than 12 months at diagnosis. Thus, in very young children with ALL (but not AML), the rearrangement status of the 11q23/MLL region supersedes age group as a determinant of treatment outcome.     

Photoacoustic analysis of proteins: volumetric signals and fluorescence quantum yields

A series of proteins has been examined using time-resolved, pulsed-laser volumetric photoacoustic spectroscopy. Photoacoustic waveforms were collected to measure heat release for calculation of fluorescence quantum yields, and to explore the possibility of photoinduced nonthermal volume changes occurring in these protein samples. The proteins studied were the green fluorescent protein (GFP); intestinal fatty acid binding protein (IFABP), and adipocyte lipid-binding protein (ALBP), each labeled noncovalently with 1-anilinonaphthalene-8-sulfonate (1,8-ANS) and covalently with 6-acryloyl-2-(dimethylamino)naphthalene (acrylodan); and acrylodan-labeled IFABP and ALBP with added oleic acid. Of this group of proteins, only the ALBP labeled with 1,8-ANS showed significant nonthermal volume changes at the beta = 0 temperature (approximately 3.8 degrees C) for the buffer used (10 mM Tris-HCI, pH 7.5) (beta is the thermal cubic volumetric expansion coefficient). For all of the proteins except for acrylodan-labeled IFABP, the fluorescence quantum yields calculated assuming simple energy conservation were anomalously high, i.e., the apparent heat signals were lower than those predicted from independent fluorescence measurements. The consistent anomalies suggest that the low photoacoustic signals may be characteristic of fluorophores buried in proteins, and that photoacoustic signals derive in part from the microenvironment of the absorbing chromophore.     

Right and left ventricular geometry and myocyte contractile processes with dilated cardiomyopathy: myocyte growth and beta-adrenergic responsiveness

OBJECTIVES: Comparison of the effects of supraventricular tachycardia-induced dilated cardiomyopathy on left and right ventricular isolated myocyte geometry and function. BACKGROUND: Chronic ventricular tachycardia and supraventricular tachycardia cause left ventricular dilation and dysfunction in humans. However, it is unknown whether supraventricular tachycardia-induced dilated cardiomyopathy is a homogenous process for both the left and right ventricles. METHODS: Dilated cardiomyopathy was induced by rapid atrial pacing (240 beats/min, 3 weeks) in 5 pigs. Five age- and weight-matched pigs served as controls. Ventricular mass was measured, myocyte dimensions were obtained, and isolated right and left ventricular myocyte contractile performance was evaluated at baseline and after beta-adrenergic receptor stimulation. RESULTS: With the development of dilated cardiomyopathy, there was no change in left ventricular mass. In contrast, right ventricular mass was increased, as was right ventricular myocyte cross-sectional area. In the control group, baseline right ventricular myocyte contractile function was increased compared to left ventricular myocytes. beta-adrenergic receptor stimulation increased myocyte contractile function in both left and right ventricular myocytes. With supraventricular tachycardia-induced cardiomyopathy, both left and right ventricular myocyte contractile function and beta-adrenergic responsiveness were reduced. CONCLUSIONS: This study demonstrated differences in left and right ventricular myocyte growth with supraventricular tachycardia-induced dilated cardiomyopathy and this differential growth response was associated with changes in contractile performance. Thus, in this model of cardiomyopathic disease, left and right ventricular growth and changes in contractile performance are not a homogenous process.