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BACKGROUND—Resection is the treatment of choice for lung cancer, but may cause impaired cardiopulmonary function with an adverse effect on quality of life. Few studies have considered the effects of thoracotomy alone on lung function, and whether the operation itself can impair subsequent exercise capacity. METHODS—Patients being considered for lung resection (n = 106) underwent full static and dynamic pulmonary function testing which was repeated 3-6 months after surgery (n =53). RESULTS—Thoracotomy alone (n = 13) produced a reduction in forced expiratory volume in one second (FEV1; mean (SE) 2.10 (0.16) versus 1.87 (0.15) l; p

The ventilatory response to exercise in patients with chronic heart failure (CHF) is greater than normal for a given work or metabolic rate (VO2). The factors that determine the ventilatory response to exercise are: 1) the CO2 production (VCO2), 2) the arterial CO2 set-point (arterial PCO2 (PaCO2) at rest), 3) the physiological dead space/tidal volume ratio (VD/VT), and 4) the change in PaCO2 during exercise. This report illustrates how each of these factors might influence the ventilatory response to exercise in CHF patients. Thirty-one CHF patients (New York Heart Association, Classes 2 and 3) were studied, 18 from Harbor-UCLA Medical Center (cycle-ergometer exercise) and 13 from Queen's University at Belfast (treadmill exercise). A group of healthy subjects matched for size, age and gender served as control subjects. Minute ventilation (VE) was 48, 88 and 43% greater in the CHF groups compared to the control population at 6 min of the 25w and 60w cycle and low level (2.5 km h-1 and 5% grade) treadmill exercise, respectively. VO2 kinetics were slower in CHF patients than the control group, the slowing being proportional to the lactate increase. However, the increase in VO2 above rest at 6 min of exercise was approximately the same for CHF and control subjects. VCO2 at 6 min increased in the CHF patients by 7% and 34% for 25 and 60 watts cycle and 19% for treadmill exercise, respectively, compared to the control group. Because PaCO2 was not measured in this study, neither CO2 set-point nor the VD/VT could be individually calculated. Because end-tidal PCO2 will decrease when PaCO2 decreases or VD/VT increases, the combined effect of PaCO2 change and increase in VD/VT could be assessed from the difference between the patient and the control group. Since PETCO2 was significantly reduced in the patient population at the end of 60w cycle exercise (32 versus 41 mm Hg), either the VD/VT was increased and/or the PaCO2 was reduced. Because the resting PaCO2 is generally normal in CHF patients, the increase in the ventilatory response to exercise in patients with CHF can best be accounted for by three physiological mechanisms: 1) an increase in VCO2 secondary to CO2 release from bicarbonate as it buffers lactic acid, 2) the reduction in PaCO2 secondary to the lactic acidosis-induced hyperventilation, and 3) an increase in the fraction of breath that is wasted (dead space). Mathematically, these factors interact so that relatively small changes in each cause large changes in VE.

During normal progressive exercise, the gas exchange anaerobic threshold occurs when CO2 production (VCO2) and ventilation (VE) increase so as to depart from a linear relationship to O2 consumption (VO2). This is thought to represent a gas exchange response to metabolic acidosis due to lactate accumulation. Patients with McArdle's disease have previously been reported to exhibit a steepened ventilatory response relative to VCO2, despite an inability to produce lactate. However, the VCO2 response has not been studied. We therefore investigated the VCO2-VO2 and VE-VO2 relationships in seven McArdle's disease patients and seven control subjects during symptom-limited maximal treadmill exercise. Analysis of gas exchange showed that whereas all control subjects had an easily identifiable anaerobic threshold, four of the patients had none and the other three displayed an attenuated threshold. The occurrence of the threshold in one patient was associated with a small rise in lactate and in another patient with an abrupt rise in leg discomfort, suggesting a pain response. Ammonia and the purine metabolite hypoxanthine were elevated during exercise in all patients, suggesting that ammonia may be a product of adenosine monophosphate degradation. Free fatty acid levels were also elevated, and a shift toward utilization of lipid may contribute to abnormal gas exchange responses. It is concluded that lactic acidosis contributes to the gas exchange anaerobic threshold but that other factors, such as discomfort, may be involved in the excess Ve seen during heavy exercise.

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE) infections cause significant morbidity and mortality among liver transplant candidates and recipients. To assess rates of MRSA and VRE colonization, we obtained active surveillance cultures from 706 liver transplant candidates and recipients within 24 h of admission to an 11-bed liver transplant ICU from October 2000 to December 2005. Patients were followed prospectively to determine the cumulative risk of MRSA or VRE infection or death by colonization status. Outcomes were assessed by Kaplan-Meier survival analysis and Cox regression and multivariate logistic regression adjusting for covariates. The prevalence of newly detected MRSA nasal and VRE rectal colonization was 6.7% and 14.6%, respectively. Liver transplant candidates and recipients with MRSA colonization had an increased risk of MRSA infection (adjusted OR = 15.64, 95% CI 6.63-36.89) but not of death (adjusted OR = 1.00, 95% CI 0.43-2.30), whereas those with VRE colonization had an increased risk both of VRE infection (adjusted OR = 3.61, 95% CI 2.01-6.47) and of death (adjusted OR = 2.12, 95% CI 1.27-3.54) compared with noncolonized patients. Prevention and control strategies, including use of active surveillance cultures, should be implemented to reduce the rates of both MRSA and VRE colonization in this high-risk patient population.

Arterial desaturation as measured using pulse oximetry may not reflect cardiorespiratory disease; other possible causes, including certain drugs, should be sought. Within the literature, examples exist of dapsone-induced methaemoglobinaemia causing diagnostic confusion, particularly where respiratory disease is a feature. Few cases have been reported that demonstrate the potential of relatively low levels of methaemoglobinaemia to upset pulse oximetry readings. We describe three examples of dapsone-induced methaemoglobinaemia emphasising the potential for low-grade methaemoglobinaemia to cause diagnostic confusion. Widespread use of the pulse oximeter indicates this problem may occur more regularly, hence there is a need for increased awareness.

Pharmacological stress testing may be used in the diagnosis of coronary artery disease when there are contra-indications to the use of conventional exercise protocols. The responses to such testing using arbutamine and to conventional treadmill exercise were compared in eight patients. Respiratory gas analysis and cardiovascular observations were performed during both tests. For an equivalent increment in heart rate, both protocols increased systolic blood pressure and serum lactate. Minute ventilation and oxygen consumption also rose during both protocols, but much more so with exercise. The end-tidal partial pressure of CO(2) [35.1 (S.D. 3. 1) to 30.8 (6.6) mmHg] and the dead space/tidal volume ratio (V(D)/V(T)) [0.37 (0.09) to 0.33 (0.08)] fell significantly during arbutamine infusion, but the respiratory exchange ratio did not change during either protocol. Oxygen pulse, a marker of stroke volume, did not change significantly after arbutamine, but rose markedly after exercise [arbutamine, 3.9 (1.1) to 3.37 (0.7) ml. min(-1).beat(-1); exercise, 4.7 (1.4) to 16.1 (4.6) ml.min(-1). beat(-1) (P0.0001 compared with baseline); difference between peak responses: P0.0001]. We conclude that arbutamine simulates some of the physiological responses to exercise, although a number of these responses are less marked than during conventional exercise, in particular cardiac output (oxygen pulse). An increase in ventilation is produced, possibly due to direct stimulation of arterial chemoreceptors. These data suggest that the main action of arbutamine is to increase central drive rather than to establish peripheral demand.

Nitric oxide (NO) is present in exhaled breath and produced by the pulmonary vascular endothelium as a potent vasodilator. Exercise is normally associated with pulmonary vasodilatation and a decrease in pulmonary vascular resistance to accommodate the increase in cardiac output. If production of NO is impaired in patients with chronic congestive cardiac failure (CCF), this might contribute to their exercise intolerance.We quantified NO production (V NO) in 12 patients with chronic stable CCF and 12 controls, at rest and during incremental cardiopulmonary exercise on a treadmill, and at a later date during constant workload exercise.Patients had reduced V NO compared with controls during incremental exercise [381 (180) vs. 777 (275) nL min-1; mean (SD); P0.0001] but at constant workload V NO was similar between the two groups [353 (124) vs. 389 (189) nL min-1; P = 0.25]. Plasma levels of nitrate, the stable end-product of NO production, were significantly higher in patients [resting value 46.1 (21.6) vs. 23.0 (10.0) microM; P = 0.004] and were not influenced by exercise.Impaired NO-mediated pulmonary vasodilatation does not appear to contribute to exercise limitation in CCF. Alternatively, the lower NO production observed during maximal exercise in the patient group compared with controls may reflect a reduced incremental response of a system that is already abnormally activated in heart failure.

In patients with acute heart failure, lung water content is increased leading to pulmonary oedema.1 This can be detected clinically and radiologically, and makes a major contribution to the severe dyspnoea characteristic of this condition. In contrast, the lung water content in stable chronic cardiac failure has not been defined, as previous studies all included patients with overt fluid overload in their analysis.2–4 We therefore carried out a pilot study with computed tomography (CT) measurement of lung water in patients with stable chronic cardiac failure, as well as some patients with acute heart failure, and compared their scans with scans from patients without evidence of heart failure. Seventeen patients with chronic cardiac failure (three women) took part in this study. The mean age was 60.4 years (range 41–79 years), mean height 1.73 m (1.58–1.97 m), and mean weight 83.3 kg (64–103 kg). Three were current smokers and four had never smoked. The cause of the heart failure was ischaemic heart disease (10 patients) or dilated cardiomyopathy (seven). All had at least one previous episode of pulmonary oedema and a mean left ventricular ejection fraction of 27% (range 15–40%) measured by echocardiography in nine and by gated blood pool scanning in eight. At the time of the study the patients had been stable …

Chronic Fatigue Syndrome appears to represent a spectrum of disorders in which a variety of pathophysiological mechanisms may operate. While the initiating event in the majority of patients is a pyrexial illness, possibly due to enterovirus infection, evidence of persisting infection or inflammatory changes in muscle and/or brain remain unconvincing. CFS patients display a definite reduced aerobic work capacity compared to normal control subjects, but this may reflect a state of deconditioning resulting from prolonged physical inactivity. They also have an altered perception of their level of exertion and premorbid fitness. The characteristic fluctuation in symptoms, with periods of relapses and partial remissions, may indicate that some central disorder of sensory perception is operational. It may be that a primary sleep disorder results in a reduced sensory threshold for afferent stimuli from muscle. This could well account for many of the subjective symptoms which patients experience. Much more research is clearly necessary if we are to achieve a better understanding of this distressing and at present enigmatic disorder.

Research conducted in several countries has shown consistent patterns of performance on ‘change’, ‘combine’ and ‘compare’ word problems involving addition and subtraction. This paper interprets these findings within a theoretical framework that emphasizes the development of empirical, logical and mathematical knowledge.

Experiments were designed to determine whether renal excretion of uric acid is achieved by the same mechanism as for renal tubular excretion of hippurates and related organic acids. Surviving slices of rabbit kidney cortex were unable to accumulate C14-urate by a concentrative mechanism. Further, entry of C14-urate into renal slices was unaffected by acetate, probenecid or anoxia in accord with earlier observations from this laboratory with non-radioactive urate. Experience with isolated perfused rat liver supports the use of this experimental method as a model of the hippurate transport system. Unlike hippurate and a large number of related organic anions, neither urate nor C14-activity derived from urate was concentrated in the bile from this preparation. Probenecid did not inhibit excretion of the small amounts of C14-activity which did appear in the bile. Urate did not compete with indigo carmine, a nonmetabolizable substrate of the hippurate transport system, for excretion into the bile. From these findings, it is concluded that urate and organic acids such as hippurate do not behave similarly in kidney or in liver. The possibility that urate might be excreted by an independent active transport mechanism is not excluded. The demonstration that renal tissues can synthesize urate from hypoxanthine raises the possibility that urate synthesis might also occur in the intact animal and might contribute to the renal clearance of uric acid.