Cognitive mapping style relates to posterior–anterior hippocampal volume ratio

As London taxi drivers acquire “the knowledge” and develop a detailed cognitive map of London, their posterior hippocampi (pHPC) gradually increase in volume, reflecting an increasing pHPC/aHPC volume ratio. In the mnemonic domain, greater pHPC/aHPC volume ratios in young adults have been found to relate to better recollection ability, indicating that the balance between pHPC and aHPC volumes might be reflective of cross‐domain individual differences. Here, we examined participants' self‐reported use of cognitive map‐based navigational strategies in relation to their pHPC/aHPC hippocampal volume ratio. We find that greater reported cognitive map use was related to significantly greater posterior, relative to anterior, hippocampal volume in two separate samples of young adults. Further, greater reported cognitive map usage correlated with better performance on a self‐initiated navigation task. Together, these data help to advance our understanding of differences between aHPC and pHPC and the greater role of pHPC in spatial mapping.     

Cardiovascular effects of microinjections of adenosine analogs into the fourth ventricle of rats

Rats were implanted with chronic indwelling cannulae into the posterior region of the fourth ventricle. After recovery from surgery, acute experiments on blood pressure were conducted under urethane anesthesia. The blood pressure and heart rate responses following administration of two adenosine analogs, NECA and L-PIA were examined. Microinjections of both analogs produced dose-dependent reductions in blood pressure and heart rate. NECA was approximately 20-fold more potent than L-PIA in reducing blood pressure and depressing heart rate. The cardiovascular effects of both analogs were antagonized by parenteral injections of caffeine. These findings show that microinjections of analogs of adenosine into the fourth ventricle can influence areas of the central nervous system involved in cardiovascular control.     

Selective antagonism of platelet-activating factor (PAF)-induced aggregation and secretion in washed rabbit platelets by CV-3988, L-652731, triazolam and alprazolam

Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine or AGEPC) is a potent phospholipid mediator elaborated by a variety of mammalian cells. CV-3988 (a unique structural analog of AGEPC), L-652731 (a lignan derivative of a natural product) and two triazolobenzodiazepines (triazolam and alprazolam) were evaluated for their ability to selectively antagonize aggregation and secretion responses in washed, [3H]serotonin-labeled rabbit platelets stimulated with graded doses of AGEPC. When 0.2 nM AGEPC was used as the stimulus, the concentration of antagonist needed for 50% inhibition (IC50) of secretion was obtained at 0.05 uM, 0.15 uM, 0.6 uM and 2.5 uM, for L-652732, CV-3988, triazolam and alprazolam, respectively. The corresponding IC50 values for aggregation were obtained at 0.2 uM, 0.1 uM, 1.5 uM and 6.5 uM, respectively. The inhibitory effects could be overcome by increasing the amount of AGEPC used to stimulate the platelets. Of the four compounds tested, L-652731 was the most potent antagonist of AGEPC-induced activation of washed rabbit platelets.     

Obstetric complications, neurodevelopmental deviance, and risk of schizophrenia

It is concluded from a review of the literature and a pilot survey that schizophrenic patients more frequently have a history of obstetric complications (OCs) than do other psychiatric patients and normal subjects. OCs are associated with increased cerebral ventricular size in both infancy and adulthood, and are more common among non-familial schizophrenic patients. Neonatal cerebrovascular events consequent upon OCs provide a mechanism to explain the increased risk of neurodevelopmental deviance and later schizophrenia.     

Persistent and reversible cardiac dysfunction among amateur marathon runners.

AIMS: Transient systolic and diastolic abnormalities in ventricular function have previously been documented during endurance sports. However, these described alterations may be limited by the techniques applied. We sought, using less load-dependent methods, to characterize both the extent and the chronology of the cardiac changes associated with endurance events. METHODS AND RESULTS: Transthoracic echocardiography (TTE) was performed prior to, immediately after, and approximately 1 month after completion of the 2003 Boston Marathon in 20 amateur athletes. TTE included two-dimensional, spectral and tissue Doppler (TD) and flow propagation velocity (V(p)). After completion of the marathon, global measures of left ventricular (LV) systolic function were unchanged (EF 59 +/- 6 vs. 61 +/- 4% post, P = 0.14), whereas TD-derived measures of LV systolic function [septal strain -23 +/- 5 vs. -17 +/- 4%, P = 0.007; septal strain rate (SR) -1.5 +/- 0.3 vs. -1.1+/- 0.2 s(-1), P = 0.007] and right ventricular (RV) systolic function (RV apical strain -33 +/- 4 vs. -27 +/- 5%, P = 0.001; RV apical SR -2.4 +/- 0.7 vs. -1.8 +/- 0.5, P = 0.002) were reduced. Significant changes in transmitral velocity (E/A ratio 2.0 +/- 0.5 vs.1.3 +/- 0.3, P = 0.005) and TD indices of LV and RV diastolic function (E(a) septal 9.5 +/- 1.8 vs. 8.1 +/- 1.2 cm/s post-marathon, P = 0.01) were also observed, indicating an inherent alteration in LV relaxation. Although all indices of LV and RV systolic function had returned to normal on follow-up, there were persistent diastolic abnormalities (RV E(a), 11.5 +/- 1.5 cm/s pre-marathon vs. 10.0 +/- 1.6 cm/s follow-up, P = 0.01). CONCLUSION: Marathon running leads to transient systolic and more persistent diastolic dysfunction of both the LV and the RV.     

Glucosamine sulfate and cartilage type II collagen degradation in patients with knee osteoarthritis: randomized discontinuation trial results employing biomarkers

OBJECTIVE: To determine whether glucosamine sulfate has an effect on cartilage type II collagen degradation in patients with knee osteoarthritis (OA). METHODS: A randomized, double blind, placebo controlled glucosamine discontinuation trial was conducted in 137 subjects with knee OA, who had had at least moderate relief of knee pain after starting glucosamine. Subjects were randomized to glucosamine at prestudy dose or placebo at an equivalent dose. Treatment was continued to Week 24 or disease flare, whichever occurred first. Serum and urine samples were collected at Weeks 0, 4, 12, and 24 or flare visit. Samples were analyzed in triplicate for 2 type II collagen degradation biomarkers: C2C epitope (COL2-3/4C(long)) and C1,2C epitope (COL2-3/4C(short)). The primary outcome was the mean change in serum and urine C1,2C/C2C ratio in the glucosamine and placebo groups from baseline to final (flare or Week 24) visit. Linear regression analyses were conducted to adjust for potential confounders. Due to non-normal distributions, the data were log-transformed (lnC1,2C/C2C). Secondary outcomes included comparison of mean change scores at final visit compared to baseline for serum and urine C1,2C and C2C in the 2 treatment groups and in Flare versus No-Flare groups. RESULTS: Baseline and final visit samples were available in 130 subjects for serum analysis and 126 subjects for urinalysis. No significant difference was seen between placebo and glucosamine groups in the serum C1,2C/C2C ratio, with a mean (SD) change from baseline to final visit of 0.8 (27.8) and -0.1 (1.8), respectively (mean difference 0.9; 95% CI -6.0, 7.7, p = 0.80). Similarly, no differences between treatment groups were seen for mean change in urine C1,2C/C2C (p = 0.82), or for mean change in C2C or C1,2C. In linear regression analysis, after adjustment for sex, radiographic severity, baseline lnC1,2C/C2C ratio, WOMAC function, and flare status, treatment was not a significant predictor of final serum or urine lnC1,2C/C2C ratio. When those who experienced flare were contrasted with those without flare, there was a nonsignificant trend toward a difference in mean baseline to final visit change score for serum C1,2C/C2C ratio (p = 0.12). In addition, in the multivariable linear regression analysis, flare status showed a borderline association with final visit serum lnC1,2C/C2C ratio (p = 0.16). CONCLUSION: No statistically significant effect of glucosamine sulfate on type II collagen fragment levels in serum or urine was observed for knee OA over 6 months. Further research is necessary to elucidate which biopathologic systems, if any, are affected by glucosamine treatment. While collagen degradation products may be of value in predicting progression, at least as defined by clinical flare, a larger dataset would be needed to prove this.     

Role of invasive electrophysiologic testing in patients with symptomatic bundle branch block

Electrophysiologic testing was performed in 112 symptomatic patients with bundle branch block. Abnormalities included HV interval 70 ms or longer (35 patients), infra-Hisian block with atrial pacing (6 patients) and sinus node dysfunction (23 patients). Inducible ventricular tachycardia occurred in 47 patients (42%). Therapy was based on the electrophysiologic test result: group I--16 patients with no therapy (normal study results); group II--34 patients with permanent pacing alone; group III--39 patients with antiarrhythmic therapy alone; and group IV--21 patients with both antiarrhythmic therapy and permanent pacing. Cumulative 4-year survival rates were 83% in group I, 84% in group II, 63% in group III and 84% in group IV (mean follow-up 2.5 years). Recurrent syncope occurred in 19% of group I, 6% of group II, 33% of group III and 19% of group IV. In symptomatic patients with bundle branch block and normal electrophysiologic test results, prognosis is good without treatment. In patients undergoing permanent pacing based on electrophysiologic testing, survival is good and rate of symptom recurrence is low. Electrophysiologic testing identifies patients with inducible ventricular tachycardia for whom antiarrhythmic therapy is indicated but who nevertheless have a poor prognosis.     

Aging, long-distance running, and the development of musculoskeletal disability. A controlled study

Four hundred ninety-eight long-distance runners aged 50 to 72 years were compared with 365 community control subjects to examine associations of repetitive, long-term physical impact (running) with musculoskeletal disability and medical service utilization in a cross-section study. Runners had less physical disability than age-matched control subjects (p less than 0.01) and maintained more functional capacity (p less than 0.001) as measured by a modified Health Assessment Questionnaire Disability Index. Runners sought medical services less often, but one third of the visits that they did make were for running-related injuries. No differences were found between groups in conditions thought to predispose to osteoarthritis and musculoskeletal disability. Ligamentous laxity and family history of arthritis were similar in both groups. Runners demonstrated better cardiovascular fitness and weighed less. Differences persisted after adjustment for age, occupation, and sex, and after inclusion or exclusion of subjects with major medical problems. Musculoskeletal disability appeared to develop with age at a lower rate in runners (0.003 units per year versus 0.028) than in community control subjects, and the decreased rate was observed with both lower extremity and upper extremity functions. These data suggest positive effects of systematic aerobic running activity upon functional aspects of musculoskeletal aging.     

Association between blood pressure, the treatment of hypertension, and cardiovascular risk factors in women

OBJECTIVE: To examine relationships of normal blood pressure (BP), hypertension and degree of BP control with cardiovascular disease (CVD) risk factors and predicted 10-year risks for coronary heart disease (CHD) and stroke. DESIGN: Cross-sectional survey. SETTING: 107 Marks and Spencer retail stores in the UK. PARTICIPANTS: 14,077 women, aged 30-64 years, screened for CVD risk factors between 1988 and 1991. MAIN OUTCOME MEASURES: Systolic (SBP) and diastolic (DBP) BP; total, high-(HDL) and low-density lipoprotein (LDL) cholesterol, ratio of total to HDL cholesterol (TC/HDL-C); triglycerides, apolipoprotein A1, apolipoprotein B, lipoprotein (a), glucose, body mass index, antihypertensive medication and predicted risks for CHD and stroke. Hypertension was defined as SBP > or = 140 mmHg and/or DBP > or = 90 mmHg and/or taking anti-hypertensive medication. Subjects were divided into normotensives with optimal (n = 6,599), normal (n = 3,170) and high normal (n = 2,184) BP levels, and hypertensives with adequate BP control (n = 228), untreated (n = 1,729) and inadequate BP control (n = 291). RESULTS: BP level was associated with other CVD risk factors among both normotensives and hypertensives. Women with inadequately controlled BP had the worst risk profile, followed by untreated hypertensives, those with adequately controlled BP and normotensives. Odds ratios for being in the top quintile of predicted 10-year CHD and stroke risks were 1, 2.7, 4.2, 8.5, 13.0, 18.9 for CHD; 1, 1.1, 5.8, 18.7, 20.6, 756 for stroke, for optimal, normal, high normal, adequate BP control, untreated and inadequate BP control groups respectively. CONCLUSIONS: Untreated hypertensives and women taking anti-hypertensive medication but with BP > or = 140/90 mmHg have the most atherogenic risk factor profiles. Effective management of BP and the associated CVD risk requires a multi-factorial approach, rather than addressing BP control in isolation.