Outcome following proximal femoral fracture in Northern Ireland.

OBJECTIVE: To study the outcome following treatment for proximal femoral fracture in elderly people. METHODS: All consecutive males and females admitted to the acute fracture service at the Royal Victoria Hospital and the Belfast City Hospital for the 3 years from 1999 to 2001 were studied. The data was collected by trained research nurses. Variables gathered included age, sex, marital status, mental state, pre-injury Barthel score and the American Society of Anaesthesiology (ASA) physical status grading. The information was gathered on admission to hospital and at four, six and 12 months after the injury. RESULTS: The total number of patients studied between January 1999 to December 2001 was 2834 of whom 77% were female and 23% were male. The mean (median) length of stay in the acute fracture service was 10.7 (9 days). The mean (median) length of stay in the rehabilitation ward was 35.3 (24 days). The 30-day mortality was 6.9%, the four-month mortality 15.6 % and one year mortality 22.3 %. Of those subjects living at home at the time of fracture 68% remained at home at one year. Factors predicting successful return home were higher mental test score, younger age, female sex, higher Barthel score, better pre-injury mobility and better ASA score. Of those able to walk independently outdoors before injury 40% regained this ability by 12 months. Factors predicting return of pre-injury mobility were poorer pre-injury mobility, younger age, higher mental test score, better ASA category, higher Barthel score, and previous residence at home. The proportion admitted from their own home and discharged by 56 days was 56%. CONCLUSION: The standardised measurement of outcome in hip fracture subjects enables comparison between units and facilitates improvement in standards of care available to the increasing number of elderly patients presenting with proximal femoral fracture.

Effect of thoracotomy and lung resection on exercise capacity in patients with lung cancer.

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<0.05). Wedge resection (n = 13) produced a non-significant reduction in total lung capacity (TLC) only. Lobectomy (n = 14) reduced forced vital capacity (FVC), TLC, and carbon monoxide transfer factor but exercise capacity was unchanged. Only pneumonectomy (n = 13) reduced exercise capacity by 28% (PVO2 23.9 (1.5) versus 17.2 (1.7) ml/min/kg; difference (95% CI) 6.72 (3.15 to 10.28); p<0.01) and three patients changed from a cardiac limitation to exercise before pneumonectomy to pulmonary limitation afterwards. CONCLUSIONS: Neither thoracotomy alone nor limited lung resection has a significant effect on exercise capacity. Only pneumonectomy is associated with impaired exercise performance, and then perhaps not as much as might be expected.

Body composition and energy expenditure of patients with chronic cardiac failure.

BACKGROUND: Patients with acute cardiac failure have excess body water, and it is commonly assumed that this is also so in patients with stable chronic cardiac failure (CCF). METHODS: To investigate this, we measured total body water (TBW) using stable isotope dilution and single-frequency bioelectrical impedance (BIA), and also extracellular volume (ECV) using bromide dilution in 12 patients with CCF and eight matched control subjects. RESULTS: TBW [kg(-1) bodyweight] was similar in the two groups [median 18O dilution 53.2% (range 46.5-57.1%) in patients vs. 54.8% (47.9-62.7) in control subjects; BIA 56.6% (42.7-73.1) vs. 58.0% (52.0-68.6)]. ECV was also similar in the two groups [0.25 Lkg(-1) (0.20-0.29) vs. 0.25 (0.19-0.35)]. There was a strong correlation between stable isotope and BIA measurements of TBW for all subjects (r = 0.76), but BIA overestimated TBW by a mean difference of 2.4 kg (limits of agreement of -4.1 kg to +8.9 kg). Body fat content was similar in the two groups, whether measured by skinfold anthropometry, whole-body densitometry or by 18O dilution. Resting energy expenditure (REE), calculated from indirect calorimetry, and total energy expenditure (TEE), calculated from the ratio of 2H to 18O elimination rate after drinking doubly labelled water, were also similar in the two groups. CONCLUSION: It is concluded that the patients with stable CCF in this study had normal ECV and TBW, and so excess body water did not account for their persistent symptoms.

Exercise responses in patients with IDDM.

OBJECTIVE: The hemodynamic, respiratory, and metabolic responses to exercise were studied in IDDM patients and control subjects to detect diabetic cardiomyopathy. RESEARCH DESIGN AND METHODS: Eight subjects aged 25-40 years with diabetes of at least 10 years' duration were compared with eight control subjects aged 21-46 years. All subjects underwent a progressive incremental bicycle exercise test with measurement of gas exchange, blood glucose, lactate, fat metabolite, and catecholamine levels and two steady-state exercise tests with measurement of cardiac output by a CO2 rebreathing method. A new first-pass radionuclide method was used to measure cardiac ejection fractions (EFs) at rest, peak exercise, and steady-state exercise. RESULTS: The peak achieved oxygen consumption was similar in the diabetic and control subjects (29.9 [25.1-34.6] and 31.4 [26.9-35.9] ml.min-1.kg-1, respectively; mean [95% CI]). There were no significant differences in heart rate, double product, ventilation, respiratory exchange ratio, or ventilatory equivalents for oxygen and CO2 during the incremental test. Glucose levels were higher in the diabetic subjects, but there were no significant differences in levels of lactate, catecholamines, free fatty acids, glycerol, or beta-hydroxybutyrate. Left ventricular EF fell from rest to peak exercise within the diabetic group (66.0% [59.6-72.4] at rest; 53.6% [45.6-61.6] at peak; P < 0.05) but this did not differ significantly from the control group (58.7% [52.3-65.1] at rest; 60.3% [48.9-71.7] at peak). Right ventricular EFs were similar in each group, and there was no reduction in peak filling rate to suggest diastolic dysfunction. The cardiac output responses to exercise were also similar in the two groups. CONCLUSIONS: There is no evidence of impairment of the exercise response in subjects with long-standing diabetes, and the apparent fall in left ventricular EF at peak exercise could be related to hemodynamic adaptation.

Non-invasive measurement of cardiac output and ventricular ejection fractions in chronic cardiac failure: relationship to impaired exercise tolerance.

1. The role of cardiac output limitation in the pathophysiology of exercise in patients with chronic failure remains undefined. During steady-state submaximal exercise, oxygen uptake is similar in patients and control subjects, but it is not known if cardiac output is also similar. We wished to determine if the reduced exercise tolerance of patients with chronic cardiac failure during such exercise is related to reduced cardiac output, or to peripheral factors. 2. Ten male patients with stable chronic failure and ten age-matched male normal controls were studied at rest and during exercise. Each subject performed a familiarization exercise test, a symptom-limited maximal exercise test and two submaximal exercise tests. Cardiac output was measured by a carbon dioxide rebreathing method. We also measured oxygen consumption, ventilation, Borg score of perceived exertion and venous lactate concentration, and ejection fractions. 3. As expected, patients had lower peak oxygen consumption [median (range) 1.18 (0.98-1.76) versus 1.935 (1.53-2.31) l/min; P < 0.001], lower peak venous lactate concentration but a similar overall level of perceived exertion. At the same submaximal workload, patients and control subjects had similar oxygen consumption [0.67 (0.59-0.80) versus 0.62 (0.52-0.82) l/min] and cardiac output [6.92 (5.79-9.76) versus 7.3 (5.99-10.38) l/min] but the patients had a greater perceived level of exertion [Borg score: 4 (1-6) versus 3 (1-5); P < 0.005], higher venous lactate concentration [1.6 (1-3.3) versus 1.14 (0.7-1.7) mmol/l; P < 0.05] and higher heart rate [106 (89-135) versus 87 (69-112) beats/ min; P < 0.005]. 4. During submaximal exercise at a similar absolute workload, patients with cardiac failure have a similar oxygen uptake and cardiac output but greater anaerobiosis and increased fatigue when compared with normal subjects. These findings appear to relate predominantly to changes that occur in the periphery rather than abnormalities of central cardiac function.

Responses of atrial natriuretic peptide and brain natriuretic peptide to exercise in patients with chronic heart failure and normal control subjects.

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are known to be elevated in patients with chronic heart failure at rest. While it is known that during exercise the circulating level of ANP increases in patients with heart failure, the response of BNP to exercise in these patients relative to control subjects is unclear. Ten patients with stable chronic heart failure and 10 normal control subjects performed symptom-limited exercise with respired gas analysis. All patients had depressed left ventricular ejection fractions (LVEF). Patients had lower peak oxygen consumption PVo2) than the control group [median (range) 1.18 (0.98-1.76) vs. 1.94 (1.53-2.31) L min-1; P < 0.001]. Circulating plasma levels of ANP and BNP were higher at rest in patients than in control subjects [ANP 335 (140-700) vs. 90 (25-500) pg mL-1; BNP 42 (25-50) vs. 20 (10-20) pg mL-1], and at peak exercise [ANP 400 (200-1000) vs. 130 (10-590); BNP 46 (40-51) vs. 20 (10-30)]. The rise in ANP at peak exercise was significant in patients compared with the resting level, but not in control subjects. For BNP, there was a significant rise in patients but no change in control subjects. The circulating plasma levels of both peptides showed a strong negative correlation with LVEF (ANP, P < 0.005; BNP, P < 0.0001) and, to a less extent, with RVEF. It is possible that BNP may give a better indication of cardiac function.

Cytokine profile in chronic cardiac failure.

Elevated tumour necrosis factor alpha (TNF-alpha) has been demonstrated in chronic cardiac failure (CCF) and may relate to severity of CCF and development of cachexia. We measured TNF receptor p55 in addition to TNF-alpha in an attempt to improve the detection rate of TNF-alpha activation, and simultaneously measured interleukin 6 (IL-6), interleukin 8 (IL-8) and C-reactive protein. Thirty-four patients with CCF and 24 control subjects were studied. Only TNF receptor p55 [6.95 (0.77-42.3) vs. 5.52 (1.50-13.36) ng mL-1 (median (range)] and IL-6 [0.335 (0-9.79) vs. 0(0-14.71) pg mL-1) were significantly elevated in patients compared with control subjects (both P < 0.05). All inflammatory markers were more frequently elevated in patients, but none correlated with any of the clinical parameters studied. Reasons for inflammatory marker elevation in CCF are uncertain, but future studies should measure the p55 TNF receptor and IL-6 in addition to TNF-alpha, to improve detection of cytokine activity.

A double blind, placebo controlled, crossover trial of D-ribose in McArdle's disease.

To determine whether seven days oral D-ribose would improve exercise tolerance in a group of 5 patients with McArdle's disease, we performed a double blind placebo controlled crossover trial. Subjects performed weekly treadmill exercise tests with expired gas analysis until their times were reproducible. They then received 60 g D-ribose daily or placebo for seven days. Exercise testing was repeated on completion of this period. A seven day washout period then followed. Subjects then performed a new baseline exercise test prior to starting the other solution. Again after seven days the exercise test was repeated. There was no significant difference between pre-treatment exercise tests for peak oxygen consumption or level of leg fatigue. Patients did not like taking the ribose and D-Ribose does not appear to be of benefit to patients with McArdle's disease.

Neuroendocrine changes in chronic cardiac failure.

Numerous hormonal and neuroendocrine changes have been described in patients with chronic cardiac failure. These affect the balance of vasodilator and vasoconstrictor factors in favour of the latter, to the detriment of the circulation. Whether this is a reaction to central cardiac (haemodynamic) abnormalities, or is an integral part of the syndrome of heart failure, remains to be determined. Catecholamine levels are increased, especially in severe heart failure, and contribute to the vasoconstriction and probably also to lethal ventricular arrhythmias. The renin-angiotensin-aldosterone system (RAAS) is also activated, causing fluid retention and further vasoconstriction. In the earlier stages, some of this increase may be iatrogenic due to the use of loop diuretics or inhibitors of angiotensin converting enzyme, but there is evidence for independent RAAS activation in more severe grades of heart failure. The role of vasoconstrictor peptides such as neuropeptide Y and endothelin is briefly considered. Counterbalancing these are vasodilator peptides, in particular atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP). The possibility of therapeutic interventions to increase circulating natriuretic hormone levels is discussed.

Erythrocyte membrane fatty acid composition as a marker of dietary compliance in hyperlipidaemic subjects.

Dietary intervention is the first treatment step in management of hyperlipidaemia, but there are few objective criteria of compliance. Whether intensive dietary intervention would produce a detectable change in erythrocyte membrane fatty acid composition which could be used as a marker of compliance was examined in 31 new hyperlipidaemic patients. Over a 6 month period, body mass index fell from 29.0 to 26.9 kg/m2 (P < 0.001) and total cholesterol by 19% from 8.16 to 6.58 mmol/l (P < 0.001). The energy derived from fat was reduced from 38.5% to 29.6% (P < 0.001), and the ratio of dietary polyunsaturated to saturated (P:S) fatty acids in the diet increased from 0.45 to 0.66 (P < 0.01). Small but significant changes were recorded in several red cell membrane fatty acids, and the P:S ratio increased from 0.91 to 1.13 (P < 0.001). It would appear, therefore, that red cell membrane changes parallel dietary changes and hence are a potential marker for compliance with dietary changes.

Variable patterns of atrial natriuretic peptide secretion in man.

Peripheral circulating levels of atrial natriuretic peptide may exhibit short-term variation compatible with a pulsatile pattern of secretion. We obtained samples every 2 min for 90 min from the antecubital vein of 16 patients with chronic cardiac failure and 13 controls. Overall levels were higher in the patients (median and quartiles 230 (125,325) vs. 26 (16,48) ng l-1; P < 0.001). In both groups there was considerable variability, with 10 (2-12) peaks, 9 (7-15) troughs (both defined as > 2 SD from the mean) and 16 (13-18) pulses (defined by computer) during the sampling period in controls, and a similar number in patients. We then carried out simultaneous sampling in the pulmonary artery, femoral artery and peripheral vein in eight subjects with normal cardiac function and six patients with impaired function due to valvular heart disease. The pattern of variability was preserved in all three sites in both groups, suggesting intermittent secretion rather than variable breakdown of the peptide in the lung. No changes in right atrial pressure or heart rate were observed to coincide with the variations, but levels of the peptide in the pulmonary artery correlated with right atrial pressure in patients (r = 0.87; P < 0.05). The mechanism of such periodicity and its pathophysiological importance remain unknown.

Respiratory gas exchange and metabolic responses during exercise in McArdle's disease.

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.