An integrated behavioral medicine approach to improving care of patients with diabetes mellitus

A detailed approach to integrating behavioral techniques into patient education, case management, and treatment evaluation of persons with diabetes mellitus is offered. The author asks a series of "what if" questions to stimulate new thinking about ways to improve patient-physician relations in overcoming problems in managing the condition, citing recent research findings in the field. Adherence to regimens, self-management, goals of an integrated diabetes program and steps along the way to achieving it, psychophysiologic mechanisms in glucose metabolism, and the function of social support are among the topics covered.     

Mice deficient for 5-lipoxygenase, but not leukocyte-type 12-lipoxygenase, display altered immune responses during infection with Schistosoma mansoni

Periovular granuloma formation during Schistosoma mansoni infection is a complex, multifaceted immunologic response. Products of arachidonic acid metabolism have been shown to contribute to this response through studies in which general inhibitors of lipoxygenase function reduce granulomatous inflammation. To determine which lipoxygenases are important for granuloma development in schistosomiasis, wild type mice or mice deficient for 5-lipoxygenase (5-LO) or "leukocyte-type" 12-lipoxygenase (12-LO) were infected with S. mansoni and studied for responses to schistosome eggs and egg antigens. At the acute stage of infection, when granuloma formation is usually maximal, 5-LO deficient mice developed smaller granulomas around liver-deposited schistosome eggs compared with wild type or 12-LO deficient mice. 5-LO mice also displayed less antibody-mediated (5 h) and cell-mediated, delayed-type (24 h) hypersensitivity to schistosome egg antigens than did the other two infection groups. In an attempt to determine possible mechanisms for the reduced inflammatory responses, we also measured hepatic mRNA levels of cytokines that have been shown to influence granuloma size (IL-4, IL-10, and IFN-gamma). The mRNA levels for IL-10 were significantly lower in 5-LO-deficient mice, but SEA-stimulated spleen cells did not demonstrate a significant difference in IL-10 production between wild type and 5-LO mice. These data suggest that 5-LO plays a role in host responses to schistosomiasis via a mechanism that cannot be explained solely by changes in expression of these cytokines.     

Is Down syndrome a risk factor for poor outcome after repair of congenital heart defects?

Down syndrome is commonly associated with significant congenital heart disease with the potential for early development of pulmonary hypertension. As such, children with Down syndrome may be at increased risk for both perioperative and long-term mortality. The purpose of this study, using data collected from a population-based outcomes study, is to analyze the potential role that Down syndrome plays in the outcome of surgically "corrected" congenital heart disease. Data were collected from a registry of all Oregon residents who, in the period 1958 to the present, had a reparative operation for one of 14 congenital cardiac malformations when younger than 18 years (N = 3965 patients). Down syndrome was present in 289 (7%) of the total registry patients. In evaluating the cardiac mortality associated with Down syndrome for each of the repaired cardiac malformations, only complete atrioventricular septal defect was associated with significantly higher perioperative (13% vs 5%) as well as higher overall late cardiac mortality through 20 years after the operation (20% vs 5%; p = 0.04). The survival outcomes for each of the other cardiac malformations were similar for children with and without Down syndrome.     

The Coriolis Interaction between the v2 = 1 and v3 = 2 States of Nitrosyl Bromide: Anomalous Quadrupole Patterns and Interstate Transitions in the Millimeter-Wave Spectrum

The millimeter-wave rotational spectra of 79BrNO and 81BrNO in the v2 = 1 and v3 = 2 vibrational states have been reinvestigated. Measurements of the rotational spectrum in the region of maximum c-type Coriolis interaction between the two states allowed the previous analysis to be extended to account for some uncommon effects. For the most perturbed transitions the nuclear quadrupole hyperfine structure arises from coupling of not only the bromine nucleus, but also the nitrogen nucleus with the rotational angular momentum. These effects were satisfactorily fitted with a Hamiltonian describing Coriolis coupling in a molecule with two quadrupolar nuclei. The successful analysis of pure rotational transitions then allowed accurate prediction of rovibrational transitions, six of which were measured for 79BrNO and four for 81BrNO. Copyright 1998 Academic Press.     

Mast cells mediate acute inflammatory responses to implanted biomaterials

Implanted biomaterials trigger acute and chronic inflammatory responses. The mechanisms involved in such acute inflammatory responses can be arbitrarily divided into phagocyte transmigration, chemotaxis, and adhesion to implant surfaces. We earlier observed that two chemokines-macrophage inflammatory protein 1alpha/monocyte chemoattractant protein 1-and the phagocyte integrin Mac-1 (CD11b/CD18)/surface fibrinogen interaction are, respectively, required for phagocyte chemotaxis and adherence to biomaterial surfaces. However, it is still not clear how the initial transmigration of phagocytes through the endothelial barrier into the area of the implant is triggered. Because implanted biomaterials elicit histaminic responses in the surrounding tissue, and histamine release is known to promote rapid diapedesis of inflammatory cells, we evaluated the possible role of histamine and mast cells in the recruitment of phagocytes to biomaterial implants. Using i.p. and s. c. implantation of polyethylene terephthalate disks in mice we find: (i) Extensive degranulation of mast cells, accompanied by histamine release, occurs adjacent to short-term i.p. implants. (ii) Simultaneous administration of H1 and H2 histamine receptor antagonists (pyrilamine and famotidine, respectively) greatly diminishes recruitment and adhesion of both neutrophils (<20% of control) and monocytes/macrophages (<30% of control) to implants. (iii) Congenitally mast cell-deficient mice also exhibit markedly reduced accumulation of phagocytes on both i.p. and s.c implants. (iv) Finally, mast cell reconstitution of mast cell-deficient mice restores "normal" inflammatory responses to biomaterial implants. We conclude that mast cells and their granular products, especially histamine, are important in recruitment of inflammatory cells to biomaterial implants. Improved knowledge of such responses may permit purposeful modulation of both acute and chronic inflammation affecting implanted biomaterials.     

Developmental aspects of dendritic cells in vitro and in vivo

Our knowledge in immunology has been dramatically increased by several excellent investigations elucidating the role of the Fas (Apo-1/CD95) receptor/ligand (FasL) system in complex immunological processes such as the acquisition of self tolerance in T cells, progression of autoimmunity, clonal deletion of activated T cells, B-cell regulation and the establishment of "immune privileged" sites such as testis or retina. In addition to these regulatory immunological activities, Fas/FasL interaction was also shown to participate in active defense mechanisms of the host against infected or transformed cells thereby inducing apoptosis in target cells. However, the same mechanism seems also to be part of an escape strategy utilized by tumor cells in various neoplastic malignancies of both hematopoetic as also non-hematopoetic origin. We ourselves were able to demonstrate that neoplastic plasma cell lines, as well as native malignant myeloma cells constitutively express FasL mRNA and protein. The FasL molecule is functionally active and able to induce programmed cell death in Fas sensitive target T cells in vitro. These target T cells were protected from programmed cell death by preincubation of T cells with a Fas-blocking monoclonal antibody (mAb) or of myeloma cells with a FasL-neutralizing mAb. respectively. Furthermore, overexpression of the caspase inhibitor, cowpoxvirus protein CrmA, also protected target T cells from being killed by myeloma cells, identifying Fas/FasL mediated signaling as the effector pathway utilized by malignant plasma cells. Our observations strongly suggest the engagement of Fas/FasL interaction in the escape strategy of this malignancy. The molecular basis of this evasive mechanism differs in essential respects from those described in melanoma, lung cancer, hepatocellular carcinoma, or astrocytoma, since downregulation of Fas or instrinsic insensitivity towards Fas-mediated signaling were not prerequisites for the occurrence of this phenomenon in Fas-sensitive multiple myeloma cell lines. However, myeloma cell lines resisted cocultivation with FasL-expressing target T cells in vitro. The aim of this review is to discuss the role of Fas/FasL interaction in the establishment of malignant disease, in the light of our findings on myeloma cells and also by drawing upon similar observations of other investigators on different kinds of tumor cells and cell lines and further to consider its possible relevance in formulating novel approaches to cancer therapy.     

Ischemic proctosigmoiditis

Rectal ischemia is rare because of excellent collateral supply. Although rectosigmoid ischemia is usually accompanied by more proximal colonic involvement, it may occur alone. METHODS: A retrospective review of all patients diagnosed as having colonic ischemia at the Mayo Clinic from 1976 to 1991 was performed. Clinical, endoscopic, radiological, and pathological data were obtained from patient charts. Patients with involvement of the rectosigmoid colon extending to no more than 30 cm above the dentate line on endoscopy were included in the study. A single radiologist reviewed CT scans and aortograms, and a single pathologist reviewed tissue specimens. RESULTS: Ten of 328 patients with ischemic colitis had isolated ischemic proctosigmoiditis. Six patients had acute ischemia (i.e., symptom duration of less than 4 wk), and four had chronic ischemia (symptoms for 4 wk or longer). Ischemic proctosigmoiditis affects elderly patients with atherosclerosis. An identifiable precipitating factor, such as a major illness or hemodynamic disturbance, was identified in four of six patients with acute ischemic proctosigmoiditis and in one of four patients with chronic ischemic proctosigmoiditis. CT revealed rectal wall thickening and/or perirectal stranding. Angiography may demonstrate atheromatous disease of the aortoiliac vessels. Acute and "chronic" presentations had similar histopathological changes. CONCLUSIONS: Ischemic proctosigmoiditis is rare. In contrast to generalized colonic ischemia, patients with acute rectal ischemia often have clearly identifiable precipitating factors. Conservative management is appropriate for uncomplicated acute ischemic proctosigmoiditis. Patients with chronic ischemic proctosigmoiditis. Patients with chronic ischemic proctosigmoiditis may develop bowel perforation necessitating a proctectomy or colonic diversion. Recognition of this entity and differentiation from idiopathic inflammatory bowel disease is important to determine appropriate therapy.     

NanoProbeArrays for the analysis of ultra-low-volume protein samples using piezoelectric liquid dispensing technology

Antibody microarrays are gaining popularity as a high-throughput technology to investigate the proteome. However, protein extracts from most body fluid or biopsy samples are available in very small volumes and are often unsuitable for large-scale antibody microarray studies. To demonstrate the potential for protein analysis with as little as a few nanoliters of sample, we have developed a new technology called NanoProbeArrays based on piezoelectric liquid dispensing for non-contact printing and probing of antibody arrays. Instead of flooding the protein sample on the antibody microarray surface, as in conventional microarray screening, a piezoelectric inkjet printer is used to dispense nanoliters of fluorescently labeled proteins over the antibody spots on the array. The ability of NanoProbeArrays to precisely identify and reliably distinguish between test proteins from different sources, without any loss of sensitivity and specificity as compared with conventional antibody microarrays, is illustrated here. The utility of NanoProbeArrays for biomarker identification in a complex biological sample was tested by detecting the cytokine interleukin-4 in serum. The significant reduction in volume of sample during NanoProbeArray analysis, as compared with conventional antibody microarrays, offers new opportunities for basic and applied proteomic research.     

Comparison of paper-and-pencil versus Web administration of the Youth Risk Behavior Survey (YRBS): Participation,data quality,and perceived privacy and anonymity

The Youth Risk Behavior Surveillance System (YRBSS) monitors priority health-risk behaviors among US high school students. To better understand the ramifications of changing the YRBSS from paper-and-pencil to Web administration, in 2008 the Centers for Disease Control and Prevention conducted a study comparing these two modes of administration. Eighty-five schools in 15 states agreed to participate in the study. Within each participating school, four classrooms of students in grades 9 or 10 were randomly assigned to complete the Youth Risk Behavior Survey questionnaire in one of four conditions (in-class paper-and-pencil, in-class Web without programmed skip patterns, in-class Web with programmed skip patterns, and “on your own” Web without programmed skip patterns). Findings included less missing data for the paper-and-pencil condition (1.5% vs. 5.3%, 4.4%, 6.4%; p < .001), less perceived privacy and anonymity among respondents for the in-class Web conditions, and a lower response rate for the “on your own” Web condition than for in-class administration by either mode (28.0% vs. 91.2%, 90.1%, 91.4%; p < .001). Although Web administration might be useful for some surveys, these findings do not favor the use of a Web survey for the YRBSS.     

Determination of glucose with glucoseoxidase-UV, using hexokinase as the reference method (author's transl)

Results obtained with the commercial test-set "GOD-UV" (Dr. Haury, München) are reported. This method permits the determination of serum-glucose within 3 minutes. The procedure is satisfactory in normal and hyperglycaemic patients. In the hypoglycaemic state, however, there is a danger of misinterpretation. The glucose oxidase-UV is compared with the hexokinase reaction.