Relationship of age and hypertension to neuropsychological test performance

Young adult (X = 29) and middle aged (X = 50) hypertensive and normotensive subjects were compared with respect to seven neuropsychological test scores derived from tests on the Halstead-Reitan battery. Age main effects, with inferior performance for the middle aged subjects, were observed for the localization and time portions of the Tactile Performance Test (TPT) and for the Trail Making A test. The multivariate age effect was significant for the composite of seven scores. A multivariate blood pressure main effect was obtained and main effect blood pressure was significant for the category test; hypertensives made more errors than normotensives. A blood pressure by age interaction was observed for finger tapping scores and the TPT-Memory scores with larger differences between hypertensives and normotensives for the younger than for the middle aged group. Results were discussed in terms of previous studies of age and hypertension with the WAIS, the Primary Mental Abilities Test and serial reaction time measures. The poor prediction of hypertensive status from individual neuropsychological test scores was emphasized and readers were cautioned not to conclude that essential hypertensives, as a group, can be characterized as brain damaged.     

On using contemporary motor theory for memory research with the aged

It was the goal of this study to determine whether there were age differences specifically associated with the ability to simultaneously execute two tasks, and whether cognitive costs correlated across different situations. Eighty-one young and 86 older adults underwent nine tasks, administered both in single and in dual conditions. Results showed large age differences in raw performances in all conditions. However, a larger cognitive cost in the older adults sample, as assessed by an Age 2 Condition interaction, was observed only for four out of the nine tasks. Furthermore, age effects were greatly diminished once performance in the single tasks was controlled for. Correlations between the dual tasks, or between the cognitive cost scores, were very low once age was partialled out. Results do not support the notion of general coordination costs and speak against a generalized increase in divided attention costs with advancing age.     

Allosteric peptide regulators of chemokine receptors CXCR4 and CXCR7

The chemokine CXCL12 and its shared seven-transmembrane receptors CXCR4 and CXCR7 regulate diseases including cancer, atherosclerosis, autoimmunity, and HIV infection, making these molecules promising drug targets. These molecules also control key processes in normal development and physiology, suggesting the need to selectively modulate CXCR4 and/or CXCR7 functions and signaling to reduce potential complications of long-term therapy. We previously identified two peptides that functioned as allosteric agonists driving CXCR4-dependent chemotaxis, providing key structural information to design a small number of additional peptides to investigate determinants of CXCL12 interactions and signaling through CXCR4 and CXCR7. In the current study, we show that the previously identified peptides only minimally activated CXCR4 signaling through the cytosolic adapter protein β-arrestin 2 and do not initiate signaling to ERK1/2. By comparison, peptides with diverse N-terminal amino acid sequences effectively activated CXCR7 signaling to β-arrestin 2. One peptide, designated as GSLW based on its N-terminal amino acids, activated CXCR7 signaling and potentiated CXCL12-CXCR7 signaling without blocking the scavenger function of CXCR7 to internalize CXCL12. These results advance our understanding of CXCR7 ligand recognition and signaling, and provide structural information to target allosteric binding sites on this receptor as chemical probes and potential therapeutic agents.     

Clinical review: What are the best hemodynamic targets for noncardiac surgical patients?

Perioperative hemodynamic optimization, or goal-directed therapy (GDT), has been show to significantly decrease complications and risk of death in high-risk patients undergoing noncardiac surgery. An important aim of GDT is to prevent an imbalance between oxygen delivery and oxygen consumption in order to avoid the development of multiple organ dysfunction. The utilization of cardiac output monitoring in the perioperative period has been shown to improve outcomes if integrated into a GDT strategy. GDT guided by dynamic predictors of fluid responsiveness or functional hemodynamics with minimally invasive cardiac output monitoring is suitable for the majority of patients undergoing major surgery with expected significant volume shifts due to bleeding or other significant intravascular volume losses. For patients at higher risk of complications and death, such as those with advanced age and limited cardiorespiratory reserve, the addition of dobutamine or dopexamine to the treatment algorithm, to maximize oxygen delivery, is associated with better outcomes.     

Does Reduction in Gastric Acid Secretion in Bariatric Surgery Increase Diet-Induced Thermogenesis?

Background: Patients who have undergone gastrectomy for benign ulcer do not develop obesity. Furthermore, morbidly obese patients who undergo biliopancreatic diversion (BPD), Roux-en-Y gastric bypass (RYGBP) and vertical banded gastroplasty (VBG) plus truncal vagotomy, may lose more weight compared with patients who undergo VBG alone. A common characteristic of the above is the reduction of gastric hydrochloric acid secretion. We investigated whether reduction in gastric acid increases dietary- induced thermogenesis because of maldigestion of foods, and this may account for the greater weight loss in the above situations. Materials and Methods: 22 volunteers without symptoms from the upper gastrointestinal tract were studied. Gastric pH was measured and resting energy expenditure (MREE), using indirect calorimetry, was determined before and 8 hours after consumption of a standard meal. Parameters were measured again after 2 months administration of proton pump inhibitors in all volunteers. Results: Although significant reduction of gastric acid secretion occurred (p<0.01), following administration of proton pump inhibitors, the fasting and postprandial MREE remained unchanged (p>0.05). Conclusions: The reduction in gastric acid secretion does not increase the energy requirements for digestion of foods and thus is neither the mechanism responsible for the increased weight loss observed after RYGBP or BPD, nor the explanation for the lean appearance of gastrectomized patients.     

Optimization of Hyperthermic Intraperitoneal Chemotherapy With Oxaliplatin Plus Irinotecan at 43°C After Compete Cytoreductive Surgery: Mortality and Morbidity in 106 Consecutive Patients

Background Peritoneal carcinomatosis (PC), which has hitherto been regarded as a lethal entity, can now be cured with surgery (treating macroscopic tumor seeding) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) (treating residual microscopic disease). The purpose of this study was to analyze the morbidity and mortality of a particular approach associating optimal (R0–R1) cytoreduction, optimal HIPEC combining oxaliplatin and irinotecan, and an optimal homogeneous intraperitoneal temperature of 43°C. Methods A total of 106 consecutive patients were included in this prospective phase 2 study. After complete resection of the PC, HIPEC was performed by the Coliseum technique with oxaliplatin (360 mg/m²) combined with irinotecan (360 mg/m²) in 2 L/m² of 5% dextrose, over 30 minutes at a real intraperitoneal temperature of 43°C. During the hour preceding HIPEC, patients received 5-fluorouracil (400 mg/m²) and leucovorin (20 mg/m²) intravenously, resulting in tritherapy. Results Postoperative mortality and morbidity rates were 4% and 66%, respectively. The most frequent complications were digestive fistula (24%), lung infection (16%), and severe hematological toxicity (11%). Statistical correlation was evidenced between morbidity and the carcinomatosis score (P = .0008), the number of resected organs (P = .0001), the duration of surgery (P = .0001), and blood loss (P = .0001). Conclusions This new approach, optimized in three respects (complete cytoreduction, combination oxaliplatin with irinotecan, and high temperature) has resulted in a relatively high but acceptable incidence of adverse events considering the expected advantage for survival.     

Depression and suicide attempt as risk factors for incident unprovoked seizures

Major depression has been shown to increase the risk for development of epilepsy, but prior studies have not evaluated whether this is due to specific symptoms of depression. We conducted a population-based case-control study of all newly diagnosed unprovoked seizures among Icelandic children and adults aged 10 years and older to test the hypothesis that major depression is a risk factor for developing unprovoked seizure and epilepsy, and to address whether specific symptoms of depression account for this increased risk. Cases were matched to the next two same sex births from the population registry. Using standardized interviews, we ascertained symptoms of major depression to make a Diagnostic and Statistical Manual, Fourth Edition (DSM-IV) diagnosis. A history of major depression was 1.7-fold more common among cases than among controls (95% confidence interval, 1.1-2.7). A history of attempted suicide was 5.1-fold more common among cases than among controls (95% confidence interval, 2.2-11.5). Attempted suicide increased seizure risk even after adjusting for age, sex, cumulative alcohol intake, and major depression or number of symptoms of depression. Major depression and attempted suicide independently increase the risk for unprovoked seizure. These data suggest that depression and suicide attempt may be due to different underlying neurochemical pathways, each of which is important in the development of epilepsy.     

Giant cell tumour of tendon sheath of the digits. A systematic review

Background  

We reviewed the literature to evaluate the demographic, clinical and histological profile of giant cell tumour of tendon sheath of the digits (GCTTSD). The overall recurrence rate and the factors affecting tumour recurrence were also assessed.