Colonic strictures in children with cystic fibrosis

PURPOSE: To determine the radiographic, clinical, surgical, and histologic findings in children with cystic fibrosis who develop strictures of the colon. MATERIALS AND METHODS: Ten children (five boys, five girls; age range, 2.5-9.0 years; mean age, 5.5 years), who were treated at the practices of the authors, were retrospectively identified and their medical records reviewed. RESULTS: Radiographic manifestations of the colonic disease included mucosal irregularity and spiculation with nodular thickening of the colonic wall and loss of normal colonic haustration. Luminal narrowing involved long segments of the colon. Longitudinal shortening of the colon was also a prominent feature. The decrease in caliber of the bowel ranged from mild narrowing to complete occlusion of the lumen. Histologic examination revealed severe submucosal fibrosis and fatty infiltration with transmural extension of the fibrosis to involve the serosa in some cases. Unlike in Crohn disease, however, acute inflammatory changes were minimal or absent. CONCLUSION: Colonic stricture in children with cystic fibrosis is due to irreversible and frequently progressive narrowing of the colonic lumen.     

INTEGRAL EQUATION APPEOACH FOZ SIHULATION-OF - HEAT AND MASS TRANSFER PROCESSES

An integral equation approach was recommended for modelling and simulation of heat and mass transfer processes. It was shown that several mixing models that have been dealt with up to now dlfferently, can be unified in a single integral equation. An effective numerical method was developed for the solution of non-linear integral equation. A construction method for the source and kernel functions were lntroduced in connection with the simulation and control of heat treatlng processes taking place in tunnel kiln and heat and mass transfer processes in tunnel dryer.

We have concluded that our method is advantageous If the slmulated process 1s slgnlficantly affected by the degree of mixing and/or the kernel function can be determined by direct measurement of the streaming phases including feedback, recirculation etc.     

Dual inhibition of human type 4 phosphodiesterase isostates by (R, R)-(+/-)-methyl 3-acetyl-4-[3-(cyclopentyloxy)-4-methoxyphenyl]-3- methyl-1-pyrrolidinecarboxylate

Purified recombinant human type 4 phosphodiesterase B2B (HSPDE4B2B) exists in both a low- and a high-affinity state that bind (R)-rolipram with Kd's of ca. 500 and 1 nM, respectively [Rocque, W. J., Tian, G., Wiseman, J. S., Holmes, W. D., Thompson, I. Z., Willard, D. H., Patel, I. R., Wisely, G. B., Clay, W. C., Kadwell, S. H., Hoffman, C. R., and Luther, M. A. (1997) Biochemistry 36, 14250-14261]. Since the tissue distribution of the two isostates may be significantly different, development of inhibitors that effectively inhibit both forms may be advantageous pharmacologically. In this study, enzyme inhibition and binding of HSPDE4B2B by (R, R)-(+/-)-methyl 3-acetyl-4-[3-(cyclopentyloxy)-4-methoxyphenyl]-3-methyl-1-pyrrolidin ecarboxylate (1), a novel inhibitor of phosphodiesterase 4 (PDE 4), were investigated. Binding experiments demonstrated high-affinity binding of 1 to HSPDE4B2B with a stoichiometry of 1:1. Inhibition of PDE activity showed only a single transition with an observed Ki similar to the apparent Kd determined by the binding experiments. Deletional mutants of HSPDE4B2B, which have been shown to bind (R)-rolipram with low affinity, were shown to interact with 1 with high affinity, indistinguishable from the results obtained with the full-length enzyme. Bound 1 was completely displaced by (R)-rolipram, and the displacement showed a biphasic transition that resembles the biphasic inhibition of HSPDE4B2B by (R)-rolipram. Theoretical analysis of the two transitions exemplified in the interaction of (R)-rolipram with HSPDE4B2B indicated that the two isostates were nonexchangeable. Phosphorylation at serines 487 and 489 on HSPDE4B2B had no effect on the stoichiometry of binding, the affinity for binding, or the inhibition of the enzyme by 1. These data further illustrate the presence of two isostates in PDE 4 as shown previously for (R)-rolipram binding and inhibition. In contrast to (R)-rolipram, where only one of the two isostates of PDE 4 binds with high affinity, 1 is a potent, dual inhibitor of both of the isostates of PDE 4. Kinetic and thermodynamic models describing the interactions between the nonexchangeable isostates of PDE 4 and its ligands are discussed.     

Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo

Genistein, found in soy products, is a phytochemical with several biological activities. In the current study, our research focused on the estrogenic and proliferation-inducing activity of genistein. We have demonstrated that genistein enhanced the proliferation of estrogen-dependent human breast cancer (MCF-7) cells in vitro at concentrations as low as 10 nM, with a concentration of 100 nM achieving proliferative effects similar to those of 1 nM estradiol. Expression of the estrogen-responsive gene pS2 was also induced in MCF-7 cells in response to treatment with a concentration of genistein as low as 1 microM. At higher concentrations (above 20 microM), genistein inhibits MCF-7 cell growth. In vivo, we have shown that dietary treatment with genistein (750 ppm) for 5 days enhanced mammary gland growth in 28-day-old ovariectomized athymic mice, indicating that genistein acts as an estrogen in normal mammary tissue. To evaluate whether the estrogenic effects observed in vitro with MCF-7 cells could be reproduced in vivo, MCF-7 cells were implanted s.c. in ovariectomized athymic mice, and the growth of the estrogen-dependent tumors was measured weekly. Negative control animals received the American Institute of Nutrition (AIN)-93G diet, the positive control group received a new s.c. estradiol (2 mg) pellet plus the AIN-93G diet, and the third group received genistein at 750 ppm in the AIN-93G diet. Tumors were larger in the genistein (750 ppm)-treated group than they were in the negative control group, demonstrating that dietary genistein was able to enhance the growth of MCF-7 cell tumors in vivo. Increased uterine weights were also observed in the genistein-treated groups. In summary, genistein can act as an estrogen agonist in vivo and in vitro, resulting in the proliferation of cultured human breast cancer cells (MCF-7) and the induction of pS2 gene expression. Here we present new information that dietary genistein stimulates mammary gland growth and enhances the growth of MCF-7 cell tumors in ovariectomized athymic mice.     

Assessment of adherence with multiple informants in pre-adolescents with spina bifida: initial development of a multidimensional, multitask parent-report questionnaire

Long-term acute care and subacute care facilities (also transitional care facilities) have evolved from the need to decrease costs associated with acute care in the hospital. As the length of stay in many medical centers has been reduced, patients are admitted to transitional care facilities to continue recovery and rehabilitation. Rehabilitation and recovery can be enhanced with the provision of optimal medical nutrition therapy. Nutrition screening is essential in identifying patients who are at risk of malnutrition or are malnourished. Nutrition assessment verifies the risk or presence of malnutrition followed by the development, implementation, and monitoring of nutrition intervention. Nutrition screening and intervention promote recovery from illness, minimize morbidity and mortality, and enhance quality of life. The goals of nutrition support are to prevent starvation-associated malnutrition, preserve lean tissue mass, support metabolic functions, and improve clinical outcomes. Oral nutrition is the preferred method of nourishment; however, specialized nutrition support is considered for patients unable to meet their nutrient requirements adequately. Enteral nutrition support is recommended when providing nutrition support however, parenteral nutrition support is used when the gastrointestinal tract can not be safely used. With appropriate intention, administration, and monitoring, nutrition support can be safely administered.     

Energetic and binding properties of DNA upon interaction with dodecyl trimethylammonium bromide

The interaction of dodecyl trimethylammonium bromide (DTAB), a cationic surfactant, with calf thymus DNA has been studied by various methods, including potentiometric technique using DTAB-selective plastic membrane electrode at 27 and 37 degreesC, isothermal titration microcalorimetry and UV spectrophotometry at 27 degreesC using 0.05 M Tris buffer and 0.01 M NaCl at pH 7.4. The free energy is calculated from binding isotherms on the basis of Wyman binding potential theory and the enthalpy of binding according to van't Hoff relation. The enthalpy of unfolding has been determined by subtraction of the enthalpy of binding from the microcalorimetric enthalpy. The results show that, after the interaction of first DTAB molecule to DNA (base molarity) through the electrostatic interaction, the second DTAB molecule also binds to DNA through electrostatic interaction. At this stage, the predom-inant DNA conformational change occurs. Afterwards up to 20 DTAB molecules, below the critical micelle concentration of DTAB, bind through hydrophobic interactions.     

Molecular biologic markers and cancer risk assessment

BACKGROUND: Malignant melanoma is the second most common vulvar malignancy. The superficial inguinal lymph nodes are the main site of metastases. Endometrial metastasis of vulvar malignant melanoma has not been previously reported. CASE: Vulvar malignant melanoma was diagnosed in a 60-year-old, postmenopausal woman. Immunohistochemical stains were positive for vimentin and S-100 protein and negative for HMB-45. Six months following vulvectomy, right inguinal lymphadenectomy and immunotherapy, curettage was performed due to postmenopausal bleeding. Histologic and immunohistochemical examinations revealed metastatic malignant melanoma with the same staining reactivity as the primary vulvar neoplasm had. Hysterectomy and bilateral salpingo-oophorectomy was performed, disclosing invasion of the endometrium and the inner two thirds of the myometrium. CONCLUSION: Only 10 other cases of endometrial metastases from malignant melanoma have been previously reported. All those cases involved a primary tumor occurring in the trunk and extremities. This is presumably the first report on endometrial and myometrial metastases from vulvar malignant melanoma.