Activity measurements support dimensional assessment

The Diagnostic and Statistical Manual approach to motor excess has been to treat it as a categorical variable whose presence functions as an inclusion criterion. Motor excess is thought to occur primarily during structured settings that maximize attentional demands. Activity is rarely measured as a dimensional attribute despite availability of a wide variety of suitable instruments for more than a decade (Tryon, 1985). The present study measured activity using electronic step counters in structured and unstructured school settings, commuting from home to school and back home, and at home for 2 consecutive weeks in 60 children selected from 450 children using Factor IV (hyperactivity) scores from the Conners Teacher Rating Scale to represent three levels of hyperactivity. Results indicate that (a) children rated as hyperactive are measurably more active than children rated as normally active in unstructured as well as structured situations, (b) measured activity correlates consistently and substantially with rated activity in unstructured and structured situations, and (c) a single activity factor characterizes measured activity in all situations except for class transitions during school. These results and other published findings support a quantitative (dimensional) rather than qualitative (categorical) approach to motor excess.     

Comparison of anion gap and strong ion gap as predictors of unmeasured strong ion concentration in plasma and serum from horses

OBJECTIVE: To compare the accuracy of anion gap (AG) and strong ion gap (SIG) for predicting unmeasured strong ion concentration in plasma and serum from horses. ANIMALS: 6 well-trained Standardbred horses undergoing high-intensity exercise (experimental study) and 78 horses and ponies that underwent i.v. administration of lactic acid or endotoxin, and endurance, submaximal, or high-intensity exercise. PROCEDURE: Anion gap was calculated as AG = (Na+ + K+) - (Cl- + HCO3-), and SIG was calculated, using the simplified strong ion model, whereby SIG (mEq/L) = 2.24 x total protein (g/dl)/(1 + 10(6.65-pH)) - AG. The relation between AG or SIG and plasma lactate concentration was evaluated, using linear regression analysis. RESULTS: Linear relations between plasma lactate concentration and AG and SIG were strong for the experimental study (r2 = 0.960 and 0.966, respectively) and the published studies (r2 = 0.914 and 0.925, respectively). The following relations were derived: AG = 1.00 x plasma lactate + 10.5; SIG = 0.99 x plasma lactate + 2.8. An AG > 15 mEq/L indicated an increased unmeasured anion concentration, whereas a SIG < -2 mEq/L indicated an increased unmeasured strong anion concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Anion gap and SIG can be used to predict plasma lactate concentration in horses. AG is accurate and clinically useful for estimating unmeasured strong ion concentration in horses with total protein concentrations within or slightly outside reference range, whereas SIG is more accurate in horses with markedly abnormal total protein concentrations and those of various ages and with various concentrations of albumin, globulin, and phosphate.     

From famine to feast: the role of methylglyoxal production in Escherichia coli

Intestinal epithelial cell differentiation is closely regulated during normal cell renewal, maturation, and malignant transformation. Since tyrosine phosphorylation influences differentiation in other cell types and has been reported to vary between crypt cells to differentiated villus tip cells, we investigated the influence of tyrosine phosphorylation in colonocyte differentiation, by using human colonic Caco-2 cells as a model and expression of the brush border enzymes alkaline phosphatase (AKP) and dipeptidyl peptidase (DPDD) as differentiation markers. We studied three tyrosine kinase inhibitors with different modes of action and specificities, viz., genistein, erbstatin analog (EA), and tyrphostin, and the tyrosine phosphatase inhibitor sodium orthovanadate. AKP- and DPDD-specific activities were assayed in protein-matched cell lysates by synthetic substrate digestion. We also correlated the effects of these agents on brush border enzyme activity with tyrosine phosphorylation of phosphoproteins by Western blotting. Genistein (5-75 mg/ml) dose-dependently stimulated AKP and DPDD with a maximal stimulation at 75 mg/ml by 158.6+/- 17.5% and 228.6+/-37.1% of control values, respectively (n=12, P<0.001). The inactive analog genistin had no effect. Tyrphostin (25 mM) similarly stimulated AKP and DPDD by 138. 6+/-6.6% and 131.8+/-1.5% of control values (n=12, P<0.001). Unexpectedly, EA (0.1-10 mM) had the opposite effect, inhibiting AKP- and DPDD-specific activity significantly at 10 mM with a maximal 14.8+/-6.4% and 26.5+/-2.5% of control values (n=12, each P<0.001). Sodium orthovanadate had a discordant effect on these two differentiation markers. Orthovanadate dose-dependently increased AKP to a maximal 188.5+/-16.1% of basal activity at 1.5 mM but decreased DPDD activity at 1.5 mM to 47.2+/-3.8% (n=9, P<0.001 each). The effects of each agent were preserved when proliferation was blocked with mitomycin C, suggesting that the modulation of phenotype by these agents was independent of any effects of proliferation. The tyrosine phosphorylation of several phosphoprotein bands was affected differently by these agents. In particular, the tyrosine phosphorylation of one 70-kDa to 71-kDa band was increased by genistein and tyrophostin but deceased by EA. The different effects of these modulators of tyrosine kinase activity raise the possibility that at least two independent enzymes or pathways regulating tyrosine phosphorylation modulate intestinal epithelial differentiation. Furthermore, tyrosine phosphorylation of the 70-kDa to 71-kDa phosphoprotein may be important in the intracellular signaling by which intestinal epithelial cell differentiation is controlled.     

The role of risk factors for periodontal disease in patients with rheumatoid arthritis

This paper summarises the methods and some of the findings of a large cohort study of dementia and cognitive decline in subjects aged over 75 years in Cambridge, particularly regarding the incidence wave. From a sample of 1968 subjects previously studied in a prevalence study in 1985-1987, survivors were restudied at 2.4 years, in a two-stage design employing the Mini; Mental State Examination (MMSE) and the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX). High incidence rates of dementia were found, which rose steeply with age, particularly for Alzheimer's disease. New minimal dementia and milder cognitive impairment were also common. Cognitive decline on the MMSE showed a near normal, non-bimodal distribution. The sample has since been restudied at intervals for a total of up to 9 years to document longitudinal cognitive change. Brains have been obtained for post mortem neuropathological and molecular biological study, particularly of the early sequential changes associated with cognitive decline and dementia.     

A new clinical classification for hospital prognosis of unstable angina pectoris

Unstable angina represents a heterogeneous spectrum of clinical entities between chronic stable angina and acute myocardial infarction. To facilitate prognostication of in-hospital outcome, we prospectively tested on a priori unstable angina classification scheme based on information available at the time of acute presentation. Prospective database enrollment at the time of emergency room presentation was performed and patients were classified into 1 of the following categories: class IA, acceleration of previous exertional angina without electrocardiographic (ECG) changes; class IB, acceleration of previous exertional angina with ECG changes; class II, new-onset exertional angina; class III, new-onset rest angina; class IV, protracted rest angina with ECG changes. The study consisted of 1,387 consecutive patients with unstable angina. Baseline demographics and aggregate in-hospital major cardiac event rates were recorded (myocardial infarction, refractory angina, and death). There was a significant increasing trend in cardiac events from class I to IV (p < 0.0001). Class IA patients had the lowest aggregate event rate at 2.7% (p = 0.0005). Paired chi-square tests of adjacent categories showed no differences in event rates for class IB and II (p = 0.3). A significantly higher rate of adverse events was seen for class III patients (20.1%, p < 0.0001). Class IV patients demonstrated the highest rate of in-hospital adverse events (42.8%, p < 0.0001). We conclude that this easily deduced, universally applicable categorization of unstable angina is highly prognostic of in-hospital adverse cardiac events and hence could have potential use for triage decisions regarding hospital admission and intensity of therapy.     

Interpretation of intraocular and serum antibody levels in necrotizing retinitis

BACKGROUND: Intraocular antibodies have been measured as a diagnostic aid in necrotizing retinitis but interpretation of results may be difficult. METHODS: Vitreous or aqueous and serum immunoglobulin G antibodies to toxoplasmosis, cytomegalovirus, herpes simplex virus I and II, and varicella zoster virus were subjected to enzyme-linked immunosorbent assay in 27 patients with necrotizing retinitis and 15 control patients. A quotient was derived quantitating the amount of excess antibody in the eye compared to serum. Different interpretative rules were analyzed to determine which yielded the highest sensitivity and specificity. RESULTS: The highest intraocular antibody relative to serum among the 4 antibodies correctly predicted the final clinical diagnosis in 21 of 27 patients, for a sensitivity of 78% and a specificity of 90%. Interpretive rules that relied on a high numeric value of the antibody quotient or did not consider the relative ranking of the four antibody quotients were less sensitive and specific because multiple antibodies were detected in most eyes. The technique was safe and rapid. CONCLUSION: Interpretation of antibody titers in intraocular fluids is facilitated by testing several relevant antibodies and comparing the results. The technique may be helpful to diagnose necrotizing retinitis and to ascertain viral cause in acute retinal necrosis.     

Testosterone worsens endothelial dysfunction associated with hypercholesterolemia and environmental tobacco smoke exposure in male rabbit aorta

OBJECTIVES: To assess the effects of interaction of sex hormones, hypercholesterolemia (HC) and environmental tobacco smoke (ETS) exposure on endothelium-dependent relaxation, we examined vascular reactivity in vitro in an animal model of atherogenesis. BACKGROUND: Animal and human studies indicate the presence of interactions between classic coronary artery disease risk factors and endothelium-dependent relaxation. Sex hormones have also been shown to influence release of endothelium-derived relaxing factor. METHODS: New Zealand White rabbits were randomized to receive either an HC diet (n = 8) or ETS exposure plus HC diet (n = 8). Eight rabbits receiving a normal diet, without exposure to ETS, served as the control group. The HC diet consisted of 3% soybean oil and 0.3% cholesterol by weight over 13 weeks. The source of ETS was sidestream smoke of 4 cigarettes/15 min, 6 h/day, 5 days/week over 10 weeks in a smoking chamber. Rabbits were killed, and fresh aortic rings were harvested and maintained in oxygenated Krebs solution in an organ bath at 37 degrees C. Rings were precontracted with norepinephrine and exposed to acetylcholine in increasing doses, and isometric tension was recorded. Rings were also exposed to physiologic concentrations (1 nmol/liter) of either 17-beta-estradiol, testosterone or progesterone before pre-contraction with norepinephrine and relaxation with acetylcholine. Endothelium-independent relaxation was studied using nitroglycerin. The surface area of the ring covered by lipids was measured by Sudan IV staining. RESULTS: HC and ETS significantly reduced endothelium-dependent relaxation (p = 0.01 and p < 0.0005, respectively) and caused atherogenesis (p < 0.0005 and p = 0.047, respectively) but did not affect endothelium-independent relaxation. Incubation with estradiol and estradiol plus progesterone did not influence endothelium-dependent relaxation. Testosterone reduced endothelium-dependent relaxation (p = 0.049) and augmented the endothelial dysfunction associated with ETS exposure and HC (p = 0.03). CONCLUSIONS: Both HC and ETS are atherogenic and impair endothelial function but do not affect endothelium-independent relaxation. Physiologic levels of estradiol and estradiol plus progesterone do not affect endothelium-dependent relaxation. Physiologic levels of testosterone impair relaxation and augment the endothelial dysfunction associated with ETS exposure and HC.     

Doctors who perform operations. A study on in-hospital surgery in four diverse geographic areas (second of two parts)

To facilitate manpower planning in the surgical field, a study was c onducted into the work loads of surgeons in various specialities in 4 different geographical areas. Surgeons in group practice and surgeons who were Board-certified specialists carried a statistically significant larger work load of surgery. The certified surgeons performed more and more complex operations. The mean operative work load increased steeply with age, reaching a maximum at 40-44 years, and fell linearly after that age. Approximately 18 years following medical school graduation were needed for a surgeon to achieve his maximum work load. The geographic factor had no appreciable effect on work loads. Tables which broke down frequencies for each major type of operation for each type of surgical specialist indicated that even commonplace operations were not frequent events on the average for any individual surgeon. It is concluded from the study that work loads are relatively low due to excessive supply of surgeons. This is of concern because there is some doubt about maintenance of surgical skills by those doctors who perform infrequent operations. The widest variation in practice was evident between ophthalmologists and thoracic surgeons, indicating that manpower planning in this field would have to be done on a specialty-by-specialty basis. 3 plans for redistributing the operative work load and reducing the number of specialist surgeons are considered.