Leg ischemia: assessment with MR angiography and spectroscopy

PURPOSE: To prospectively determine reproducibility of magnetic resonance (MR) angiography and MR spectroscopy of deoxymyoglobin in assessment of collateral vessels and tissue perfusion in patients with critical limb ischemia (CLI) and to follow changes in patients undergoing intramuscular vascular endothelial growth factor (pVEGF)-C gene therapy, percutaneous transluminal angioplasty, supervised exercise training, or no therapy. MATERIALS AND METHODS: Study and gene therapy protocols were approved, and all patients gave written informed consent. To determine repeatability and reproducibility, seven patients underwent MR angiography and five underwent MR spectroscopy. The techniques were used to judge disease progress in 12 other patients with or without therapy: MR angiography to help determine change in visualization of collateral vessels and MR spectroscopy to help assess change in perfusion at proximal and distal calf levels. MR angiographic results were subjectively analyzed by three blinded readers. Intraobserver variability was expressed as 95% confidence interval (CI) (n=7); interobserver variability, as kappa statistic (n=15). Reexamination variability of MR spectroscopy was given as 95% CI for subsequent recovery times, and correlation with disease extent was calculated with Kendall taub rank correlation. Fisher-Yates test was used to correlate changes with pressure measurements and clinical course. RESULTS: Intraobserver and interobserver concordance was sensitive for detection of collateral vessels. Intraobserver agreement was 85.7% (95% CI: 42.1%, 99.6%). Interobserver agreement was high for small collateral vessels (kappa=0.74, P <.001) and fair for large collateral vessels (kappa=0.36, P=.002). MR spectroscopy was reproducible (95% CI: +/-26 seconds for proximal, +/-21 seconds for distal) and showed a correlation with disease extent (proximal calf, taub=0.84, P <.001; distal calf, taub=0.68, P=.04). Small collateral vessels increased over time (P=.04) but did not correlate with pressure measurements and clinical course. Recovery time correlated with clinical course (proximal calf, P=.03; distal calf, P=.005). CONCLUSION: MR angiography and MR spectroscopy of deoxymyoglobin can help document changes in visualization of collateral vessels and tissue perfusion in patients with CLI.

Endogenous and synthetic MMP inhibitors in CNS physiopathology.

Matrix metalloproteinases (MMPs, including the membrane-type MMPs (MT-MMPs)), a disintegrin and metalloproteinase (ADAM), and ADAM with thrombospondin motifs belong to the metzincins, a subclass of metalloproteinases that contain a Met residue and a Zn(2+) ion at the catalytic site necessary for enzymatic reaction. MMP proteolytic activity is mainly controlled by their natural tissue inhibitors of metalloproteinase (TIMP). A number of synthetic inhibitors have been developed to control deleterious MMP activity. The roles of MMPs and some of their ECM substrates in CNS physiology and pathology are covered by other chapters of the present volume and will thus not be addressed in depth. This chapter will focus (i) on the endogenous MMP inhibitors in the CNS, (ii) on MMP and TIMP regulations in three large classes of neuropathologic processes (inflammatory, neurodegenerative, and infectious), and (iii) on synthetic inhibitors of MMPs and the perspective of their use in different brain diseases.

Role of ovarian cancer antigen CA125/MUC16 in development and cancer

Cancer antigen 125 (CA125) is a tumor antigen that is routinely used to monitor the disease progress and the outcome of treatment in ovarian cancer patients. Elevated serum levels of CA125 are detected in over 80% of epithelial ovarian cancer patients. CA125 is a high molecular weight (>1M Dalton) mucin-type glycoprotein encoded by the MUC16 gene on human chromosome 19. Although MUC16 has served as the best serum marker for monitoring growth of ovarian cancer, roles for MUC16 in normal physiology and ovarian cancer are largely unknown. To understand the biological functions of MUC16, I characterized a mouse Muc16 homolog on chromosome 9 by means of expression pattern profiling, phenotype analysis of Muc16 knockout mice, and in vitro and in vivo studies of Muc16 null transformed ovarian surface epithelial (OSE) cells. ^ The mouse Muc16 homolog shares a conserved genomic structure with human MUC16. In addition to being expressed in mouse ovarian cancer, mouse Muc16 mRNA and protein were expressed in the mesothelia covering the heart, lung, ovary, oviduct, spleen, testis, and uterus. The conserved genomic structure and expression pattern of mouse Muc16 to human MUC16 suggests that mouse Muc16 is the ortholog of human MUC16. To understand the biological functions of Muc16, I generated Muc16 knockout mice. Muc16 knockout mice were viable, fertile and normal by one year of age. However, between 18 and 24 months of age, Muc16 knockout mice developed various tissue abnormalities such as ovarian cysts and tumors of the liver and other peritoneal organs. To determine the role of MUC16 in ovarian cancer progression, I established Muc16 null transformed ovarian surface epithelial (OSE) cell lines, following the same method to develop mouse model of epithelial ovarian cancer (Orsulic et al., 2002). Loss of Muc16 did not affect cell morphology, cell proliferation rate, or tumorigenic potential. However, Muc16-null OSE cells showed decreased attachment to extracellular matrix proteins as well as to primary mouse peritoneal mesothelial cells. Peritoneal mesothelia are the most frequent implantation sites of ovarian cancer. Furthermore, a pilot transplantation assay suggests that Muc16 null transformed OSE cells formed less disseminated tumors in the peritoneal cavity compared to wild-type OSE cells. ^ In conclusion, these results demonstrate that MUC16 is not required for normal mouse development or reproduction, but plays important roles in tissue homeostasis, ovarian cancer cell adhesion and dissemination. This study provides the first in vivo evidence of the roles of MUC16 in development, as well as ovarian cancer progression and dissemination. These studies offer valuable insights into possible mechanisms of ovarian cancer development and potential molecular targets for ovarian cancer treatment. ^

Sida y mujer : un análisis prospectivo de las causas de la infección del VIH/SIDA en las mujeres

El presente informe es el resultado de la investigación prospectiva realizada en mujeres infectadas por VIH/SIDA como tema de tesis de Magíster Políticas Sociales y Gestión Local defendida el 25 de noviembre de 2002 en el aula magna de la Facultad de Ciencias Políticas y Sociales, UNC. El SIDA no es sólo una enfermedad biológica sino que tiene una fuerte incidencia en lo social. La intención de este trabajo es despertar la inquietud para que las personas se movilicen a trabajar en la prevención y la asistencia, buscando respuestas alternativas que le faciliten al ser humano la posibilidad de tener una vida más digna. Las estadísticas nacionales demuestran una marcada feminización de esta epidemia. Las formas que asume la sexualidad son muy variadas y están determinadas por el tiempo y lugar donde vivimos. Las mujeres sufren una falta de contención de sus parejas sexuales con escasa toma de conciencia de la posibilidad de progresión de la enfermedad si no se utilizan métodos de barrera, que está íntimamente relacionado con la falta de educación sexual, también en el varón. Como conclusión, podemos decir que el 63,9% de las mujeres no utilizan métodos anticonceptivos debido a temores y prejuicios provocados por la falta de educación sexual. El 75,3% proviene de la negativa del varón a usar preservativo y el 100 % de las mujeres, a pedir el uso del preservativo por vergüenza o miedo. Todo esto nos está demostrando el poco diálogo con sus parejas sexuales y, por parte del hombre, la no protección de la mujer como madre, compañera y miembro útil de la sociedad.

Reação de genótipos de cafeeiro à Hemileia vastatrix e à Cercospora coffeicola

Coffee plants were introduced in Brazil in the Northern State of Para around 1727. Two major diseases have affected coffee trees in the country. One is rust, caused by fungus Hemileia vastatrix and accountable for production losses up to 50%. The other one is Cercospora leaf spot, caused by fungus Cercospora coffeicola endemic to all Brazilian coffee farms and, therefore, economically critical due to production losses both in the plant nursery and in the field. Availability of resistant varieties has been a constant challenge for breeders. Research programs play an important role in the search for new resistant and/or tolerant genotypes, since over time plants can become susceptible to new, genetically variable races of pathogens. This study aimed to evaluate the incidence and severity of such diseases, the resistance of different coffee genotypes to H. vastatrix and C. coffeicola pathogens, as well as the productivity of said genotypes in dense planting system. The experimental design consisted of randomized blocks, with twelve genotypes (treatments) and two replications (blocks). SISVAR® program was used to analyze data and compare them building on Scott-Knott test and Tukey’s test with a probability of 5%. Disease incidence and severity percentage were assessed for both Cercospora leaf spot and rust. Means were used to calculate the area under the disease progress curve (AUDPC) of both diseases. As to rust, the most resistant genotypes were H586-6, IBC 12, and H556-7 H567-6. As to Cercospora leaf spot and productivity, no statistical differences were found across genotypes. The dense planting system did not impair plant development, but favored disease evolution given the microclimate it produces.

Micronutrient contents in healthy and Crinipellis perniciosa infected tissues of Theobroma grandiflorum.

Micronutrient contents in leaf and branch tissues of cupuassu plants (Theobroma grand iflorum) infected by Crinipellis perniciosa, the causal agent of witches' broom disease, were determined to support further studies on the effect of nutritional status in the disease progress. Lower contents of boron and manganese and higher content of copper were found in infected leaf tissues. There was not any statistical difference in the copper content of branch tissues, even though higher copper content was found in healthy branches than in healthy leaf tissues. No changes in contents of iron and zinc in healthy of infected tissues were detected.

The Coronary Heart Disease National Service Framework: Building on excellence,maintaining progress - Progress report for 2008

This report details the progress which has been made in implementing the Coronary Heart Disease National Service Framework in the eight years since its publication.

Back to the future in Chagas disease: from animal models to patient cohort studies, progress in immunopathogenesis research

Despite the wealth of information generated by trans-disciplinary research in Chagas disease, knowledge about its multifaceted pathogenesis is still fragmented. Here we review the body of experimental studies in animal models supporting the concept that persistent infection by Trypanosoma cruzi is crucial for the development of chronic myocarditis. Complementing this review, we will make an effort to reconcile seemingly contradictory results concerning the immune profiles of chronic patients from Argentina and Brazil. Finally, we will review the results of molecular studies suggesting that parasite-induced inflammation and tissue damage is, at least in part, mediated by the activities of trans-sialidase, mucin-linked lipid anchors (TLR2 ligand) and cruzipain (a kinin-releasing cysteine protease). One hundred years after the discovery of Chagas disease, it is reassuring that basic and clinical research tends to converge, raising new perspectives for the treatment of chronic Chagas disease.

La maladie de Fabry chez l'adulte: aspects cliniques et progrès thérapeutiques [Fabry disease in adulthood: clinical aspects and therapeutic progress].

INTRODUCTION: Fabry disease is an X-linked recessive abnormality of glycosphingolipid metabolism that is due to deficiency of the lysosomal enzyme alpha-galactosidase A. CURRENT KNOWLEDGE AND KEY POINTS: A majority of hemizygous men develop severe multisystemic disease (classic form), dominated by renal failure, progressive neurological and cardiac involvement. Nevertheless, some affected men retain sufficient enzyme activity and long remain asymptomatic (atypical form); their main manifestation is hypertrophic cardiomyopathy. Female heterozygous carriers are usually asymptomatic; 15% of them, however, have severe involvement of one or several organs. Laboratory, histologic and molecular diagnosis identifies 100% of hemizygous and over 80% of heterozygous subjects. FUTURE PROSPECTS AND PROJECTS: With developments in molecular genetics, it is now possible to produce the human recombinant enzyme alpha-galactosidase A. Two recent studies had proven that this therapeutic approach was able to be clinically and histologically effective in men. In addition, the results of a trial of gene therapy in a Fabry gene knocked-out mouse appear promising.

Ion channel genes and human neurological disease: Recent progress, prospects, and challenges

What do epilepsy, migraine headache, deafness, episodic ataxia, periodic paralysis, malignant hyperthermia, and generalized myotonia have in common? These human neurological disorders can be caused by mutations in genes for ion channels. Many of the channel diseases are “paroxysmal disorders” whose principal symptoms occur intermittently in individuals who otherwise may be healthy and active. Some of the ion channels that cause human neurological disease are old acquaintances previously cloned and extensively studied by channel specialists. In other cases, however, disease-gene hunts have led the way to the identification of new channel genes. Progress in the study of ion channels has made it possible to analyze the effects of human neurological disease-causing channel mutations at the level of the single channel, the subcellular domain, the neuronal network, and the behaving organism.

Medicine, disease, and death; being an enquiry into the progress of medicine as a practical art.

Microfilmed for preservation

Control of foot-and-mouth disease. Report of special subcommittee to the Committee on Appropriations, United States Senate, on study of pernicious effect of foot-and-mouth disease as it exists in Mexico and elsewhere, progress of program to prevent entry of the disease into the United States, the most effective methods of combating and controlling the disease and the proper location for the authorized research facilities.

Kenneth S. Wherry, chairman of subcommittee.