The syndrome of senile gait

Summary Infrared computed stroboscopic photometry was used to quantify the kinematic profiles of walking in 10 elderly patients with symmetrical neurological disturbances of gait and in 19 age-matched neurologically healthy people. Clinical examination of the patients revealed similar profiles of walking even though their diagnoses were vascular dementia (2), normal pressure hydrocephalus (2), Alzheimer dementia with possible normal pressure hydrocephalus (2), mixed Alzheimer and vascular dementia (1), peripheral neuropathy (1), Alzheimer dementia with parkinsonian features (1), and un determined (1). Quantitatively, the patients' gait kinematics deviated greatly from control values, but these deviations were statistically attributable to reductions in stride. We suggest that many gait disturbances in elderly people are similar, regardless of etiology, because the characteristics of these gait disturbances are heavily veiled by nonspecific stride-dependent changes that comprise the syndrome of senile gait.     

Morphine place conditioning is differentially affected by CCKA and CCKB receptor antagonists.

In the present study we have examined the interaction between the selective cholecystokinin (CCK)A and CCKB receptor antagonists, devazepide and L365-260 on morphine conditioned place preference (CPP). Using an unbiased procedure, morphine (1.5 mg/kg) produced a reliable CPP which was observed irrespective of the conditioning compartment type. Pretreatment with devazepide (0.001-0.01 mg/kg s.c.) produced a dose related attenuation of this response. At higher doses (0.1-1 mg/kg) this antagonism became variable and dependent on the training compartment with blockade only observed when conditioning was to the white/rough textured environment. This profile has also been reported for the serotonin (5-HT)3 receptor antagonist ondansetron. The CCKB antagonist L365-260 (0.000001-0.01 mg/kg) failed to antagonize the morphine CPP, if anything a mild potentiation was observed. To study this further we examined the interaction between L365-260 (0.01 mg/kg) and a subthreshold dose of morphine (0.3 mg/kg). At these doses neither drug elicited CPP, however when co-administered a significant CPP was recorded. Finally, L365-260 at 1 mg/kg induced a mild but significant CPP when administered alone. These results suggest a differential role of CCK receptor subtypes on reward-related behaviour and complement previous studies suggesting bimodal effects of CCK systems on mesolimbic dopamine function.     

Neuroticism and the pain-mood relation in rheumatoid arthritis: insights from a prospective daily study.

For 75 consecutive days, 54 Ss with rheumatoid arthritis supplied daily reports of their mood and joint pain. After aggregating daily reports, the relation between chronic mood and chronic pain remained statistically significant when controlling for neuroticism, depression, disease activity, disability, and characteristic responses to increasing pain. Findings of a path analysis suggest that (a) individuals higher in neuroticism experience more chronic distress regardless of their responses to pain, their pain intensity, and depressive symptomatology, and (b) the relation between neuroticism and chronic pain is mediated by the propensity of high-neuroticism individuals to catastrophize their pain. Within-subject analyses that controlled for autocorrelation and linear trends in the time series revealed that 40% of the Ss experienced significantly worse moods on more painful days. Although individuals higher in neuroticism reported more intense pain and more negative mood, their daily mood was less strongly linked to their daily pain.     

A Bayesian approach to aid in formulary decision making: incorporating institution-specific cost-effectiveness data with clinical trial results.

Pharmacy and therapeutics committees commonly cite a lack of generalizability as a reason for not incorporating cost-effectiveness information into decision making. To address this concern, many committees undertake site-specific economic evaluations, which are often limited by small sample sizes and nonrandomized designs. We show how 2 complementary approaches were used to minimize these limitations in an economic evaluation of abciximab at 1 institution. Using a propensity score methodology, we selected patients who did not receive abciximab for the comparison cohort. Then, we adopted a Bayesian, hierarchical, random-effects model to integrate site-specific and clinical trial data. We applied the posterior distributions of effectiveness with local cost data in a traditional decision-analytic model. In 74% of the simulations, abciximab was cost-effective at 1 institution at the $50,000 per life year saved threshold, assuming a 50:50 split of patients undergoing coronary stenting and angioplasty. Among patients undergoing coronary stenting, the cost-effectiveness ratio of the addition of abciximab was at or below the $50,000 per life year saved threshold in 66.0% of the simulations.     

Cerebral vascular effects of angiotensin II: new insights from genetic models.

Very little is known regarding the mechanisms of action of angiotensin II (Ang II) or the consequences of Ang II-dependent hypertension in the cerebral circulation. We tested the hypothesis that Ang II produces constriction of cerebral arteries that is mediated by activation of AT1A receptors and Rho-kinase. Basilar arteries (baseline diameter approximately 130 microm) from mice were isolated, cannulated and pressurized to measure the vessel diameter. Angiotensin II was a potent constrictor in arteries from male, but not female, mice. Vasoconstriction in response to Ang II was prevented by an inhibitor of Rho-kinase (Y-27632) in control mice, and was reduced by approximately 85% in mice deficient in expression of AT1A receptors. We also examined the chronic effects of Ang II using a model of Ang II-dependent hypertension, mice which overexpress human renin (R+) and angiotensinogen (A+). Responses to the endothelium-dependent agonist acetylcholine were markedly impaired in R+A+ mice (P<0.01) compared with controls, but were restored to normal by a superoxide scavenger (PEG-SOD). A-23187 (another endothelium-dependent agonist) produced vasodilation in control mice, but no response or vasoconstriction in R+A+ mice. In contrast, dilation of the basilar artery in response to a NO donor (NONOate) was similar in R+A+ mice and controls. Thus, Ang II produces potent constriction of cerebral arteries via activation of AT1A receptors and Rho-kinase. There are marked gender differences in cerebral vascular responses to Ang II. Endothelial function is greatly impaired in a genetic model of Ang II-dependent hypertension via a mechanism that involves superoxide.     

Non-operative management of retroperitoneal fibrosis

It is generally recognized that in many patients the ureteric obstruction and other manifestations of non-malignant retroperitoneal fibrosis will respond to treatment with corticosteroids. However, most surgeons are reluctant to use steroids as the primary treatment for patients with this condition, mainly because of the risk of mismanagement of malignant retroperitoneal fibrosis. Our experience in the care of 17 patients with non-malignant retroperitoneal fibrosis has led us to believe that an initial non-surgical approach is both safe and preferable.     

Reperfused myocardial infarctions on T1- and susceptibility-enhanced MRI: Evidence for loss of compartmentalization of contrast media

The purpose of this study was to characterize the contrast caused by a susceptibility MRI contrast agents, on spin echo T₂-weighted imaging of reperfused myocardial infarction. Our interest in this model focused on the expected requirement that such agents be compartmentalized in the tissue to cause signal loss on spin echo images, a condition which may not be present in reperfused infarcted myocardium. Accordingly, nine rats were subjected to 2 h of left coronary artery occlusion followed by 3 ± 0.5 h of reperfusion prior to administration of contrast media. Three sets of MR images were acquired: (a) baseline axial images at the midventricle, both T₁-weighted (TR/TE = 300/20) and T₂-weighted (TR/TE = 1500/60); (b) T₁-weighted images after administering a T₁-enhancing agent, Gd-DTPA-BMA (0.2 mmol/kg), to document that contrast media is delivered to the reperfused infarction; and (c) T₂-weighted images after administering the susceptibility agent, Dy-DTPA-BMA (1.0 mmol/kg). Gadolinium-enhanced T₁ images depicted reperfused infarction as regions with greatly enhanced signal intensity compared with unin-farcted myocardium, indicating that contrast agent was delivered to the infarcted zone. Dysprosium-enhanced T₁ images depicted the injury as a region of persistent signal intensity relative to depletion of signal in normal myocardium, consistent with failure of the contrast agent to cause signal loss. Similar infarction sizes were observed for unenhanced T₂-weighted images (33 ± 5%), gadolinium-enhanced T₁ weighted images (36 ± 5%) and postmortem staining (30 ± 6%); strong correlations (r > 0.9) were noted in comparisons of these data. Dysprosium-enhanced images exhibited a smaller region of differential signal presumed to be infarction (20 ± 5%, P < 0.05) and weak correlations (r < 0.75) with the other measurements. We conclude that the smaller infarction depicted on dysprosium-enhanced images is a subregion of the true infarction in which myocardial necrosis is sufficiently advanced that the agent is homogeneously distributed throughout all tissue compartments, preventing T₂*-dependent phase loss on spin echo images.     

Variation in evoked potential measures over the menstrual cycle: A pilot study

Nancy Kluck, Scan J. O'Connor, Victor M. Hesselbrock, Allan Tasman and Donald Maier, Lance Bauer: Variation in Evoked Potential Measures Over the Menstrual Cycle: A Pilot Study. Prog. Neuro. Psychopharmacol. Biol. Psychiat. 1992. 16(6): 901–911.

1. 1. The P3 component of a visual event related potential (ERP) was studied for five consecutive weeks in six women with normal menstrual cycles. Serum concentrations of luteinizing hormone (LH), estradiol (E2) and progesterone were studied during the same period.

2. 2. Increases in P3 amplitude, although nonsignificant, were noted in the week preceding onset of menses.

3. 3. No significant changes in reaction times to target/nontarget stimuli were noted over the same time period.