A pilot study evaluating predictors of postoperative outcomes after major abdominal surgery: Physiological capacity compared with the ASA physical status classification system.

BACKGROUND: This pilot study compared the risk predictive value of preoperative physiological capacity (PC: defined by gas exchange measured during cardiopulmonary exercise testing) with the ASA physical status classification in the same patients (n=32) undergoing major abdominal cancer surgery. METHODS: Uni- and multivariate logistic regression models were fitted to measurements of PC and ASA rank data determining their predictive value for postoperative morbidity. Receiver operating characteristic (ROC) curves were used to discriminate between the predictive abilities, exploring trade-offs between sensitivity and specificity. RESULTS: Individual statistically significant predictors of postoperative morbidity included the ASA rank [P=0.038, area under the curve (AUC)=0.688, sensitivity=0.630, specificity=0.750] and three newly identified measures of PC: PAT (% predicted anaerobic threshold achieved, <75% vs > or =75%), DeltaHR1 (heart rate response from rest to the anaerobic threshold), and HR3 (heart rate at the anaerobic threshold). A two-variable model of PC measurements (DeltaHR1+PAT) was also shown to be statistically significant in the prediction of postoperative morbidity (P=0.023, AUC=0.826, sensitivity=0.813, specificity=0.688). CONCLUSIONS: Three newly identified PC measures and the ASA rank were significantly associated with postoperative morbidity; none showed a statistically greater association compared with the others. PC appeared to improve predictive sensitivity. The potential for new unidentified measures of PC to predict postoperative outcomes remains unexplored.

Exercise capacity of rats remains unaffected by a chronic pressure overload.

OBJECTIVE: The aim was to determine if the adaptive responses of the myocardium to a chronic pressure overload affected cardiovascular performance when evaluated under conditions of increased functional demand. METHODS: Selected female rats were made hypertensive by abdominal aortic constriction. After eight weeks of aortic constriction, cardiovascular responses and work performance were measured during a maximal treadmill exercise bout. RESULTS: Aortic constriction increased mean arterial pressure and the relative quantity of the slow ATPase myosin isoform, V3, relative to untreated controls (p < 0.05). Both groups had similar oxygen consumptions (VO2), heart rates (HR), and oxygen pulses (VO2/HR) at rest and throughout the exercise test. Both groups reached their VO2 max at the same exercise duration and exercise intensity (40.4 m.min-1). Soleus citrate synthase activity was not different between the groups. CONCLUSIONS: These similarities in work capacity, VO2, oxygen pulse, and muscle oxidative capacity suggest (1) that cardiovascular and exercise capacity can both be maintained in spite of the presence of a chronic pressure overload; (2) that after two months of aortic constriction the heart appears to be in a compensated stage of adaptation; and (3) that the cardiac myosin isoenzyme profile may have little direct effect on cardiovascular functional capacity.

Metabolism of deoxynucleosides by lymphocytes in long-term culture deficient in different purine enzymes.

The metabolism of 8-14C-labelled 2'-deoxyadenosine (dAR) and 2'-deoxyguanosine (dGR) has been investigated using lymphocytes in long-term culture transformed by Epstein-Barr (EB) virus (B-cells) from eight patients with different inherited purine enzyme defects. The use of such lines enabled accurate mapping of the route of metabolism by acting as a 'trap' for the radiolabel at specific points. With either substrate (25 microM) most of the label was recovered in the medium. Using dAR, less than 30% of the radiolabel was incorporated into cellular nucleotides. For dGR, values were less than 18%. Studies with dAR alone confirmed the principal route of metabolism was to hypoxanthine, with further metabolism (by lines with intact salvage pathways) to ATP and GTP in the ratio of approximately 4:1. Lack of accumulation of deoxyinosine in the purine nucleoside phosphorylase (PNP) deficient line, or hypoxanthine in the hypoxanthine guanine phosphoribosyltransferase (HGPRT) deficient line, using dAR together with the adenosine deaminase (ADA) inhibitor 2'-deoxycoformycin (dCF) at 10 microM, confirmed the effectiveness of ADA inhibition. Nevertheless, some ATP was still formed by all lines in the presence of dCF by a route as yet unknown. Only the ADA deficient lines formed dATP with dAR alone. However, some dATP was formed by all lines in the presence of dCF. A partially HGPRT deficient line formed extremely high dATP levels, well in excess of those formed by the T-cell line CEM. Studies with dGR revealed some interesting differences, a large proportion of the substrate being metabolized predominantly to xanthine by most enzyme deficient lines. In the PNP deficient line most of the substrate remained unmetabolized, but some dGTP was formed. No other enzyme deficient line formed any dGTP--with or without the PNP inhibitor 8-aminoguanosine (8-NH2GR)--with one exception. Again this was the partially HGPRT deficient line, which with the inhibitor again formed more dGTP than the T-cell line. Within the cells most of the substrate was metabolized to GTP, except in the PNP, and totally HGPRT deficient lines. Levels of GTP formed were not altered by the inhibitor, reflecting the lack of effective PNP inhibition by 8-NH2GR. Some counts were also found in ATP and IMP, confirming the existence of this route in mammalian cells of lymphoid origin. The results also support previous studies by us using cell lines with intact purine pathways, which demonstrated that, contrary to current beliefs, some B-cell lines are capable of accumulating high levels of deoxynucleotides.(ABSTRACT TRUNCATED AT 400 WORDS)

Human B lymphocytes and thymocytes but not peripheral blood mononuclear cells accumulate high dATP levels in conditions simulating ADA deficiency.

Inherited adenosine deaminase (ADA) deficiency is associated with a lymphospecific cytotoxicity affecting both dividing and non-dividing cells. The metabolic basis for this was investigated using different cell types and the potentially toxic metabolite 2'-deoxyadenosine (dAR) in short-term experiments under physiological conditions simulating ADA deficiency (1 mM Pi 8.7 microM dAR). In the uncultured cells, [8-14C] dAR alone was metabolized almost completely only by thymocytes and tonsil-derived B-lymphocytes. The greater percentage of counts (greater than 75%) were in the medium (deoxyinosine, hypoxanthine). Cellular counts were predominantly in adenine nucleotides, and to a lesser extent guanine nucleotides. Interestingly, both thymocytes and tonsil-derived B-lymphocytes, and a partially ADA deficient B lymphoblast line, accumulated detectable amounts of dATP even in the absence of ADA inhibition. Peripheral blood lymphocytes (PBMs) did not, and showed little dAR metabolism. In experiments simulating ADA deficiency varying amounts of 2'-deoxycoformycin (2'dCF) were needed to completely inhibit ADA (20-60 microM), with thymocytes requiring the highest amount. ADA inhibited thymocytes and tonsillar B-lymphocytes accumulated very high dATP levels, which were sustained to an equal extent by both over a 60-min period; PBMs accumulated the lowest values. Results in cultured cells reflected findings in previous studies. Some counts were also found in ATP by a route excluding ADA or PNP. These results again question the hypothesis that B-cells are more resistant than T-cells to the toxic effects of dAR because of an inability to accumulate and sustain elevated dATP levels and underline the lack of comparability between enzyme activity in intact as distinct from lysed cells. They cast doubt on the validity of cultured cells as a model for ADA deficiency and suggest the observed toxicity in some instances might result from altered ATP or GTP pools through inadequate ADA inhibition. They indicate that combined immunodeficiency in ADA deficiency could relate to an equal sensitivity of B-cells and T-cell precursors to the toxic effects of dATP accumulation.

Both acute and chronic exercise enhance in vivo ethanol clearance in rats.

Rates of ethanol clearance were measured at rest and with acute exercise in four groups of female Sprague-Dawley rats. Two groups were trained to run on a motor-driven rodent treadmill at 27 m/min, 1 h/day, 5 days/wk and were given a nutritionally balanced liquid diet; one of these groups received 35% calories as ethanol whereas in the other, sucrose was isocalorically substituted for the ethanol. Appropriate sedentary and nonethanol controls were also used. Clearance of a 1.75-g/kg ethanol dose injected intraperitoneally was determined by measuring ethanol levels in the blood each hour and utilizing these values in the Widmark equation (R. Teschke, F. Moreno, and A. Petrides, Biochem. Pharmacol. 30: 1745-1751, 1981) for calculating whole-body ethanol clearance. Rates of ethanol clearance were determined for each rat at 4 and 7 wk of training. The clearance tests at 4 wk included a 60-min period of running exercise, whereas the tests 3 wk later were conducted at rest. The results indicate that both acute exercise and exercise training can increase rates of in vivo ethanol clearance. In addition, the chronic exercise appeared to increase in vitro ethanol metabolism by hepatic microsomes without altering in vitro hepatic alcohol dehydrogenase activity.

Exercise alters cardiac myosin isozyme distribution in obese Zucker and Wistar rats.

Recent evidence suggests that exercise training may significantly increase the expression of the cardiac myosin isozyme V1 in the diabetic heart, a change associated with improved cardiac functional capacity. To test this hypothesis, cardiac myofibrillar adenosinetriphosphatase (ATPase) activity and myosin isozyme profiles were determined in trained and sedentary male hyperinsulinemic obese Zucker (OZT, OZS) and obese Wistar (OWT, OWS) rats. Lean sedentary (LZS, LWS) animals served as age-matched controls. Myofibrillar ATPase activity and the relative quantity of the high-ATPase isozyme V1 was significantly lower in both strains of sedentary obese rats than in the respective lean sedentary controls (P less than 0.05). Both 5 (OZT) and 10 wk (OWT) of moderate treadmill training increased these markers of cardiac myosin biochemistry in the obese animals (P less than 0.05). Thus, endurance exercise training remodels the cardiac isomyosin profile of hyperinsulinemic rats and, in doing so, may enhance cardiac contractility and functional capacity. Such changes may reflect an improvement in glucose availability and utilization in these hearts.

Effects of visual and auditory cues on gait in individuals with Parkinson's disease.

The purpose of this study was to determine if combining visual and auditory cues has a greater effect on the gait pattern of patients with Parkinson's disease (PD) than the cues applied individually. Twenty-four individuals with idiopathic PD were recruited. Patients, while off antiparkinsonian medications, were measured on a 7.62-m walkway during two trials for each of four conditions performed in random order: without cues, with a visual cue, with an auditory cue and with both cues simultaneously. The auditory cue consisted of a metronome beat 25% faster than the subject's fastest gait speed. Brightly colored parallel lines placed along the walkway at intervals equal to 40% of a subject's height served as the visual cue. Average gait speed, cadence and stride length were calculated for each condition. Gait velocity, cadence and stride length significantly improved (p<005) when cues were used. Visual and auditory cues improved gait performance in patients with PD, but they did so in different ways. Auditory cueing significantly improved cadence, but visual cueing improved stride length. The simultaneous use of auditory and visual cues did not improve gait significantly more than each cue alone.

Allopurinol in renal failure and the tumour lysis syndrome.

This paper illustrates several important points relating to the use of allopurinol in renal failure, or situations of purine overproduction: It is very easy to give too much allopurinol. Most of the side effects (bone marrow depression, exfoliative dermatitis, etc) are the result of overdosage due to the retention of oxipurinol, an effect exaggerated by thiazide diuretics. Monitoring of plasma oxipurinol levels (ideally less than 100 mumol/l) by high-pressure liquid chromatography is helpful for adjusting dosage in renal failure. Some estimate of the anticipated purine excess is equally vital in deciding dosage during tumour lysis if the risk of urate nephropathy is not to be substituted for the certainty of xanthine nephropathy. In this situation the use of allopurinol may even be questioned. Patients with HGPRT deficiency are exquisitely sensitive to allopurinol, and careful monitoring of the effect on urinary purine levels is essential if xanthine colic is to be avoided.

Altered erythrocyte nucleotide patterns are characteristic of inherited disorders of purine or pyrimidine metabolism.

This paper compares erythrocyte nucleotide levels in patients with eight different inherited purine or pyrimidine enzyme defects identified amongst a variety of patients referred predominantly for investigation of severe neurological abnormalities, or immunodeficiency syndromes. Characteristic nucleotide patterns were identified only in the six disorders (four involving purine and two pyrimidine metabolism) where there was clinical evidence of cellular toxicity. They were frequently related to the accumulation of abnormal metabolites in body fluids. These erythrocyte studies have demonstrated the following. 1. ATP depletion is not an invariable feature of adenosine deaminase (ADA) deficiency, but the accumulation of the deoxyribonucleotides dATP, or dGTP, is diagnostic of ADA, or purine nucleoside phosphorylase (PNP) deficiency, respectively. The early accumulation of dATP in foetal blood is a valuable aid to prenatal diagnosis of ADA deficiency. 2. GTP depletion appears to reflect the degree of CNS involvement in hypoxanthine-guanine phosphoribosyltransferase and PNP deficiency, as well as PP-ribose-P synthetase superactivity. Other diagnostic changes involving increased pyrimidine sugars and increased or decreased NAD levels, or ZTP in Lesch Nyhan erythrocytes, show no consistent correlation with the clinical manifestations. 3. These altered nucleotide levels afford a novel means for carrier detection of the X-linked defect associated with aberrant PP-ribose-P synthetase activity, where no other test is yet available. Measurement of erythrocyte nucleotide levels thus provides a simple and rapid aid to diagnosis and may sometimes be essential for determining prognosis, carrier detection, or monitoring therapy. These characteristic 'fingerprints' may give some insight into the mechanism by which the abnormal gene product produces disease. Such grossly altered nucleotide levels could also result in loss of erythrocyte flexibility, increased destruction and hence the anaemia, or other clinical manifestations, observed in some disorders.

Morderate diabetes alters myosin isoenzyme distribution in cardiac but not skeletal muscle of male rats.

Diabetes is known to alter the myosin phenotype of striated muscle, but the impact of the same diabetic state on different types of striated muscles remains unknown. Therefore, this study determined the myosin isoenzyme profile in the left ventricle, soleus, plantaris, and extensor digitorium longus (EDL) of young male rats made moderately diabetic with streptozotocin, (45 mg/kg, ip). Eight weeks after the single streptozotocin injection, tissues were collected and subsequently electrophoretically analyzed for native myosin isoenzyme distribution. Skeletal muscles were additionally analyzed for myosin heavy chain distribution. Neither the native myosin isoform nor the myosin heavy chain (MHC) distribution profiles of the skeletal muscles were altered by the diabetic state. In contrast, the high ATPase cardiac isoform, VI, was significantly replaced by the low ATPase isoform, V3 (p < 0.05). These results demonstrate that striated muscle responds to a moderate diabetic state in a limited and muscle specific fashion. Significantly, the change in the cardiac myosin isoform profile is comparable to that which occurs in a more severe diabetic state.

Effects of exercise and ethanol on liver mitochondrial function.

Rates of ADP stimulated respiration for various substrates were determined in mitochondria isolated from the livers of female Sprague-Dawley rats following 8 weeks of treatment with daily swimming, ethanol consumption, or both. All rats were fed an American Institute of Nutrition (AIN) type liquid diet with the ethanol treated rats receiving 35% of the calories as ethanol. Chronic exposure to ethanol depressed both state 3 respiration with glutamate as a substrate and cytochrome oxidase activity. Respiratory control ratios and P:O ratios, however, were unaffected by the ethanol exposure. Exercise alone had no effect on hepatic mitochondrial function. There were also no significant alterations in oxidative function of hepatic mitochondria from rats which were endurance-trained by swimming while receiving the ethanol diet. This lack of alteration in mitochondrial function was in spite of the fact that these rats consumed an identical amount of ethanol as those which incurred mitochondrial dysfunction. These results indicate that regular exercise has the potential to attenuate the ethanol induced decline in hepatic mitochondria.

Sodium pivalate reduces cardiac carnitine content and increases glucose oxidation without affecting cardiac functional capacity.

This study determined how selected functional, metabolic, and contractile properties were impacted by sodium pivalate, a compound which creates a secondary carnitine deficiency. Young male rats received either sodium pivalate (20 mM, PIV) or sodium bicarbonate (20 mM, CONTR) in their drinking water. After 11-12 weeks cardiac function and glucose oxidation rates were measured in isolated, perfused working heart preparations. Hearts were also analyzed for carnitine content, activities of hexokinase (HK), citrate synthase (CS), and B-hydroxyacyl CoA dehydrogenase (HOAD), and myosin isoenzyme distribution. Sodium pivalate treatment significantly reduced cardiac carnitine content and increased glucose oxidation but did not alter cardiac functional capacity. HK activity was increased in the PIV group (p < 0.05), and HOAD activity decreased (p < 0.05). CS activity and myosin isoform distribution (VI > 85%) remained unchanged. These results demonstrate that pivalate treatment of this duration and the accompanying carnitine deficiency shift cardiac substrate utilization without compromising cardiac functional capacity.

dATP accumulation and ATP depletion in platelets in adenosine deaminase deficiency: significance for the immune response?

High levels of dATP and dADP, accompanied by ATP depletion, were found in the platelets of two ADA-deficient children with severe combined immunodeficiency (SCID). In vitro studies demonstrated that even normal platelets had the ability to make dATP from deoxyadenosine (dAR) under physiological conditions. This capability was greatly enhanced by conditions simulating ADA deficiency. These results question whether the platelet has a specific role in the normal immune response.

ATP formation from deoxyadenosine in human erythrocytes: evidence for a hitherto unidentified route involving adenine and S-adenosylhomocysteine hydrolase.

A novel route of ATP formation has been identified using erythrocytes from patients deficient in four different enzymes associated with ATP formation. It entails prior adenine production from deoxyadenosine (or adenosine) in a reaction involving S-adenosylhomocysteine hydrolase. The postulated route has been demonstrated in human erythrocytes which, unlike other human cells, cannot form ATP from IMP. It is based on studies by others using purified S-adenosylhomocysteine hydrolase preparations in vitro. The results provide the first confirmation that this reaction occurs in intact human cells in vitro and thus most probably in vivo. This adenine production is normally masked in intact cells by further metabolism to ATP. Clinical significance for such a route is suggested by the fact that some adenosine analogues with potent oncostatic and antiviral properties also release adenine (or analogues) in vitro.

Prevalence and sociobehavioral correlates of tobacco use among Hispanic children: the Tobacco Resistance Activity Program.

To examine tobacco use patterns and its sociobehavioral correlates among Hispanic in-school youth, a tobacco use and knowledge survey was administered to 660 children from fourth through sixth grade classes, of which 69% (n = 453) were of Hispanic origin. Male Hispanics were more exposed to previous tobacco use (38% vs. 20%, p < .01), reported more current smoking, had more smoking friends, received more cigarette offers, and wanted to try a cigarette compared to females (all p < .05). Also, more previous alcohol use was noted in the previous tobacco users, indicating its potential as a "gateway drug." From multivariate analyses, being offered cigarettes was the strongest environmental indicator of previous tobacco usage, followed by having adult smokers in the house, smoking friends, (all p < .01), and being around other smoking youth (p < .05). This study offers additional knowledge about factors that may cause Hispanic youth to initiate smoking, and suggests the need to address peer and social influences in school-based substance abuse programs.

Effect of educational kinesiology on static balance of learning disabled students.

Educational Kinesiology is a movement-based program designed to enhance academic performance and may also influence performance of motor skills. The purpose of this study was to determine whether the Educational Kinesiology techniques of repatterning and/or integration movements affected static balance of 60 learning disabled students, ranging in age from 7 to 11 yr. Subjects were matched on age and sex and assigned to one of three groups: control, movement, or repatterned. Children in the repatterned group received a 10-min. individual session of combined arm and leg movements coordinated with eye-placements prior to the start of the 6-wk. program. Both treatment groups then participated in a movement program for 5 min. twice a day, 5 days a week for 6 wk. The control group received no exposure to these special techniques. Static balance was pretested and posttested in each group using the Modified Stork Stand test. A one-way analysis of variance indicated a significant difference between groups. A Scheffé post hoc test showed that the repatterned group improved more than the movement group, who in turn improved more than the control group.

Functional performance status of hematopoietic SCT recipients in the sub-acute phase of recovery.

This study assessed the functional capacity of sub-acute SCT recipients using validated physical performance tests, including 6-min walk distance, repeated sit-to-stand time and 50-ft walk time, and compared these outcomes with those reported for a heterogeneous oncology population. The medical records of 80 consecutive sub-acute SCT recipients not receiving corticosteroids were retrospectively reviewed for demographic, medical and anthropometric information, and outcomes for these physical performance tests administered at the time of initial physiotherapy evaluation. Measures of central tendency, 95% confidence intervals, unpaired t-tests and correlation coefficients were calculated using a SPSS statistical package. SCT recipients completed the 50-ft walk in 10.66+/-4.43 s, repeated sit-to-stand trial in 4.16+/-1.82 s and walked 400.2 m in 6 min. For the timed tests, SCT recipients were approximately twice as fast as a heterogeneous group of oncology patients and walked approximately 50% further in 6 min. No overlap in the 95% confidence intervals for the two groups was observed for any of the tests. These results (1) suggest that reference values describing the functional capacity of a heterogeneous oncology population underestimate the functional capacity of SCT recipients and (2) provide clinically useful reference values for assessing functional capacity of sub-acute SCT recipients referred for physiotherapy.