Task-Induced Brain Activity Patterns in Type 2 Diabetes: A Potential Biomarker for Cognitive Decline

Patients with type 2 diabetes demonstrate reduced functional connectivity within the resting state default mode network (DMN), which may signal heightened risk for cognitive decline. In other populations at risk for cognitive decline, additional magnetic resonance imaging abnormalities are evident during task performance, including impaired deactivation of the DMN and reduced activation of task-relevant regions. We investigated whether middle-aged type 2 diabetic patients show these brain activity patterns during encoding and recognition tasks. Compared with control participants, we observed both reduced 1) activation of the dorsolateral prefrontal cortex during encoding and 2) deactivation of the DMN during recognition in type 2 diabetic patients, despite normal cognition. During recognition, activation in several task-relevant regions, including the dorsolateral prefrontal cortex and DMN regions, was positively correlated with HbA_1c and insulin resistance, suggesting that these important markers of glucose metabolism impact the brain’s response to a cognitive challenge. Plasma glucose ≥11 mmol/L was associated with impaired deactivation of the DMN, suggesting that acute hyperglycemia contributes to brain abnormalities. Since elderly type 2 diabetic patients often demonstrate cognitive impairments, it is possible that these task-induced brain activity patterns observed in middle age may signal impending cognitive decline.     

Expression of modulators of extracellular matrix structure after anterior cruciate ligament injury

The ability of the anterior cruciate ligament (ACL) to heal after injury declines within the first 2 weeks after ACL rupture. To begin to explore the mechanism behind this finding, we quantified the expression of genes for collagen I and III, decorin, tenascin‐C, and alpha smooth muscle actin, as well as matrix metalloproteinase (MMP)‐1 and ‐13 gene expression within multiple tissues of the knee joint after ACL injury in a large animal model over a 2‐week postinjury period. Gene expression of collagen I and III, decorin, and MMP‐1 was highest in the synovium, whereas the highest MMP‐13 gene expression levels were found in the ACL. The gene expression for collagen and decorin increased over the 2 weeks to levels approaching that in the ligament and synovium; however, no significant increase in either of the MMPs was found in the provisional scaffold. This suggests that although the ACL and synovium up‐regulate both anabolic and catabolic factors, the provisional scaffold is primarily anabolic in function. The relative lack of provisional scaffold formation within the joint environment may thus be one of the key reasons for ACL degradation after injury.     

Inhibition of Intra-Abdominal Adhesions: A Comparison of Hemaseel APR and Cryoprecipitate Fibrin Glue

Our previous studies demonstrated fibrin glue (FG) prepared from cryoprecipitate (cryo) inhibits intra-abdominal adhesions in rats. A new FG, Hemaseel APR, is Food and Drug Administration (FDA) approved for hemostasis during cardiac surgery and splenic trauma. This study was undertaken to determine if Hemaseel FG prevents intra-abdominal adhesions, and to compare it to cryo FG. Forty-five rats underwent laparotomy. Bilateral peritoneal-muscular defects were created. Polypropylene mesh was sewn into each defect with a running silk suture. The bowel was abraded with gauze. The rats were then randomized to mesh covered with Hemaseel FG, cryo FG, or control. On postoperative day 7, the severity of adhesions were graded by percentage of mesh covered by adhesion (0-100%) and degree of adhesion (0-3). The mean percentage of mesh covered by adhesion was 9% for Hemaseel FG, 43% for cryo FG (p = .005), and 65% for the controls (p < .0001). The mean density adhesion score was 0.5 for Hemaseel FG, 1.2 for cryo FG (p = .04), and 2.1 for the controls (p < .0001). In the Hemaseel FG group, 77% of patches had no adhesions, compared with 37% in the cryo FG group (p = .004) and 13% in the controls (p < .0001). Thus, Hemaseel FG significantly decreases intra-abdominal adhesions, and is more effective than cryo FG.     

Physical activity and colon cancer: confounding or interaction?

PURPOSE: Although physical activity has been consistently inversely associated with colon cancer incidence, the association of physical activity with other diet and lifestyle factors that may influence this association is less well understood. Confounding and effect modification are examined to better understand the physical activity and colon cancer association. METHODS: Based on hypothesized biological mechanisms whereby physical activity may alter risk of colon cancer, we evaluated confounding and effect modification using data collected as part of a case-control study of colon cancer (N = 1993 cases and 2410 controls). We examined associations between total energy intake, fiber, calcium, fruit and vegetables, red meat, whole grains as well as dietary patterns along with cigarette smoking, alcohol consumption, BMI, and use of aspirin and/or NSAIDs and physical activity. RESULTS: No confounding was observed for the physical activity and colon cancer association. However, differences in effects of diet and lifestyle factors were identified depending on level of physical activity. Most striking were statistically significant interactions between physical activity and high-risk dietary pattern and vegetable intake, in that the relative importance of diet was dependent on level of physical activity. The predictive model of colon cancer risk was improved by using an interaction term for physical activity and other variables, including BMI, cigarette smoking, energy intake, dietary fiber, dietary calcium, glycemic index, lutein, folate, vegetable intake, and high-risk diet rather than using models that included these variables as independent predictors with physical activity. In populations where activity levels are high, the estimate of risk associated with high vegetable intake was 0.9 (95% CI 0.6-1.3), whereas in more sedentary populations the estimate of risk associated with high vegetable intake was 0.6 (95% CI 0.5-0.9). CONCLUSIONS: Physical activity plays an important role in the etiology of colon cancer. Its significance is seen by its consistent association as an independent predictor of colon cancer as well as by its impact on the odds ratios associated with other factors. Given these observations, it is most probable that physical activity operates through multiple biological mechanisms that influence the carcinogenic process.     

Donor Kidney Exchanges

Kidney transplantation from live donors achieves an excellent outcome regardless of human leukocyte antigen (HLA) mismatch. This development has expanded the opportunity of kidney transplantation from unrelated live donors. Nevertheless, the hazard of hyperacute rejection has usually precluded the transplantation of a kidney from a live donor to a potential recipient who is incompatible by ABO blood type or HLA antibody crossmatch reactivity. Region 1 of the United Network for Organ Sharing (UNOS) has devised an alternative system of kidney transplantation that would enable either a simultaneous exchange between live donors (a paired exchange), or a live donor/deceased donor exchange to incompatible recipients who are waiting on the list (a live donor/list exchange). This Regional system of exchange has derived the benefit of live donation, avoided the risk of ABO or crossmatch incompatibility, and yielded an additional donor source for patients awaiting a deceased donor kidney. Despite the initial disadvantage to the list of patients awaiting an O blood type kidney, as every paired exchange transplant removes a patient from the waiting list, it also avoids the incompatible recipient from eventually having to go on the list. Thus, this approach also increases access to deceased donor kidneys for the remaining candidates on the list.     

Acute-phase-proteins and parameters of humoral immunity in patients with advanced Hodgkin's disease

Summary Serum concentrations of acute-phase-proteins C-reactive protein (CRP), ₁-antitrypsin (AAT), ₁-acid glycoprotein (AGP) as well as levels of immunoglobulins G, A and M and of complement components C3 and C4 were evaluated in 15 patients with advanced (stages III and IV) Hodgkin's disease. Of these patients 9 suffered from B symptoms including pruritus, night sweats and fever. While all patients had highly increased concentrations of CRP and AAT and 11 patients also had elevated levels of AGP in their sera, these concentrations were significantly (P<0.001) reducible by the administration of chemotherapy. Patients with B symptoms also had significantly higher concentrations of CRP (P<0.02), AAT (P<0.05) and AGP (P<0.05) in their sera than patients without. Plasmapheresis which was performed in 3 patients did not achieve a long-lasting reduction of serum concentrations of any acute-phase-protein tested. Complement components C3 and C4 exhibited a similar behaviour as acute-phase-proteins in that they were elevated in patients with B symptoms and reducible by the administration of chemotherapy (P<0.001 and P<0.02, respectively). We conclude that serum concentrations of CRP, AAT and AGP can serve as useful markers for the assessment of tumour activity in patients with advanced Hodgkin's disease. Whereas the concentrations of immunoglobulins G and A in patients were comparable to normal controls, IgM was significantly (P<0.05) reduced in patients who had received chemotherapy, but not in those who were newly diagnosed and hat not received any treatment. Thus, chemotherapy lowered serum concentrations of IgM without influencing levels of IgG and IgA.Supported in part by the Anton Dreher Memorial Donation for Medical Research     

Pedestrian traffic injuries in Mexico: a country update

Road traffic injuries in general and pedestrian injuries in particular are a major public health problem in Mexico, especially in large urban areas. Analysis of mortality and road crashes at the national level was done using routine data recorded on death certificates. Fatality rates for different age groups were estimated by region for the year 2000. These data were supplemented by a cross-sectional study of pedestrian injuries in Mexico City based on death certificates information for pedestrians who lived and died in Mexico City between 1994 and 1997. Participant observation of physical spaces where crashes occurred was carried out. The spaces were filmed and in-depth interviews of survivors conducted. Road traffic crashes were responsible for approximately 17,500 deaths in Mexico during 2000. The mean age of the victims was 37 years. Mexico lost an average of 30 years of productive life for each individual who died in a traffic crash--525,000 years in 2000. An estimated 9500 (54.3%) of all fatalities were pedestrians, and for every pedestrian death there were 13 others who sustained nonfatal injuries requiring medical care. The overall crude mortality rate for pedestrian injuries in Mexico City was 7.14 per 100,000 (CI 6.85-7.42). A concentration of deaths was observed in 10 neighborhoods at specific types of street environments. The underlying factors included dangerous crossings and the absence or inadequacy of pedestrian bridges, as well as negative perceptions of road safety by pedestrians. In conclusion, this study demonstrates the importance of elucidating the underlying contextual determinants of pedestrian injuries.     

Bilateral plasmacytoma of the breast: a case report

Plasmacytoma of the breast is a rare condition that may occur as a solitary finding or in association with multiple myeloma. Of the cases of plasmacytoma of the breast that have been described, nearly half have been bilateral. We report a case of bilateral plasmacytoma of the breast detected on a routine screening mammogram in a patient with a recent diagnosis of multiple myeloma.     

Evaluation of fluorodeoxyglucose positron emission tomography imaging in metastatic transitional cell carcinoma with and without prior chemotherapy

INTRODUCTION: This study was designed to determine the value of fluorodeoxyglucose (FDG) positron emission tomography (PET) in the evaluation of metastatic transitional cell carcinoma (TCC). METHODS: Fifty-eight FDG PET scans were performed on 46 consecutive patients with TCC. Results were correlated with radiologic, pathologic, and histologic findings in these patients and the sensitivity of PET for detecting malignancy in untreated TCC patients (n = 48) was compared to the sensitivity in patients who had undergone prior chemotherapy (n = 10). RESULTS: Of 48 scans in patients who had no prior systemic chemotherapy, 10 had increased uptake in proven metastatic TCC lesions and 3 PET studies failed to reveal metastatic TCC (sensitivity 76.9%). In patients free of metastatic disease, 33 revealed no abnormal uptake and 1 study revealed a suspicious area in a patient free of metastases (specificity = 97.1%). However, in 10 patients imaged after receiving chemotherapy, the sensitivity fell to 50% for the detection of histologically confirmed residual/recurrent tumor by PET. CONCLUSIONS: FDG PET detects increased metabolic activity. After chemotherapy, viable cancer cells may still be present but with a diminished metabolic rate. As a result, PET imaging is often useful in the evaluation of untreated metastatic TCC metastasis but should be interpreted with caution in patients who have received prior chemotherapy.