The effect of the menstrual cycle and hyperglycaemia on hormonal and metabolic responses during exercise.

PURPOSE: Variations in substrate metabolism have been identified in women during continuous steady-state aerobic exercise performed at the same relative intensity throughout discrete phases of the menstrual cycle, although some evidence exists that this is abolished when carbohydrate is ingested. This investigation examined the effects of a supraphysiologic exogenous glucose infusion protocol, administered during two phases of the menstrual cycle (follicular and luteal) in eumenorrheic women to identify differences between metabolic, hormonal and substrate oxidative responses. METHODS: During the experimental conditions, blood glucose was infused intravenously at rates to "clamp" blood glucose at 10 mM in seven healthy females (age 20 ± 1 y, mass 55.0 ± 4.1 kg, [Formula: see text] 40.0 ± 1.8 ml/kg/min). Following 30 min of seated rest, participants exercised on a cycle ergometer for 90 min at 60% [Formula: see text]. During the rest period and throughout exercise, blood metabolites and hormones were collected at regular intervals, in addition to expired air for the measurement of substrate oxidation. RESULTS: Significant differences between ovarian hormones and menstrual phase were identified, with estrogen significantly higher during the luteal phase compared to the follicular phase (213.28 ± 30.70 pmol/l vs 103.86 ± 13.85 pmol/l; p = 0.016), and for progesterone (14.23 ± 4.88 vs 2.11 ± 0.36 nmol/l; p = 0.042). However, no further significance was identified in any of the hormonal, metabolite or substrate utilisation patterns between phases. CONCLUSION: These data demonstrate that the infusion of a supraphysiological glucose dose curtails any likely metabolic influence employed by the fluctuation of ovarian hormones in eumenorrheic women during moderate exercise.

Elevated core and muscle temperature to levels comparable to exercise do not increase heat shock protein content of skeletal muscle of physically active men.

AIM: Exercise-associated hyperthermia is routinely cited as the signal responsible for inducing an increased production of heat shock proteins (HSPs) following exercise. This hypothesis, however, has not been tested in human skeletal muscle. The aim of the present study was to therefore investigate the role of increased muscle and core temperature in contributing to the exercise-induced production of the major HSP families in human skeletal muscle. METHODS: Seven physically active males underwent a passive heating protocol of 1 h duration during which the temperature of the core and vastus lateralis muscle were increased to similar levels to those typically occurring during moderately demanding aerobic exercise protocols. One limb was immersed in a tank containing water maintained at approximately 45 degrees C whilst the contra-lateral limb remained outside the tank and was not exposed to heat stress. Muscle biopsies were obtained from the vastus lateralis of both legs immediately prior to and at 48 h and 7 days post-heating. RESULTS: The heating protocol induced significant increases (P < 0.05) in rectal (1.5 +/- 0.2 degrees C) and muscle temperature of the heated leg (3.6 +/- 0.5 degrees C). Muscle temperature of the non-heated limb showed no significant change (P > 0.05) following heating (pre: 36.1 +/- 0.5, post: 35.7 +/- 0.2 degrees C). Heating failed to induce a significant increase (P > 0.05) in muscle content of HSP70, HSC70, HSP60, HSP27, alphaB-crystallin, MnSOD protein content or in the activity of superoxide dismutase and catalase. CONCLUSIONS: These data demonstrate that increases in both systemic and local muscle temperature per se do not appear to mediate the exercise-induced production of HSPs in human skeletal muscle and suggest that non-heat stress factors associated with contractile activity are of more importance in mediating this response.

Energy balance in early breast cancer patients receiving adjuvant chemotherapy.

Weight gain is a common problem amongst women receiving adjuvant chemotherapy for early breast cancer. We undertook a study to determine the causes of this weight gain. Prospective measurements of body mass and composition (skinfolds, bioelectrical impedance, total body potassium), energy balance (resting energy expenditure dietary intake, and physical activity), were determined in 17 women during and in the 6 months after commencing adjuvant chemotherapy. Women gained significant amounts of weight (5.0 +/- 3.8; p < 0.01) and body fat (7.1 kg +/- 4.5; p < 0.01) over the year. Waist circumference (5.1 +/- 4.5 cm; p < 0.01) and abdominal skinfold (16.2 +/- 10 mm; p < 0.01) were also increased but there was a decline in fat free mass (FFM); 1.7 +/- 2.5 kg. Women due to receive adjuvant chemotherapy had a greater resting energy expenditure (REE) compared with healthy subjects (n = 21); 100.5 +/- 8.0% Harris Benedict compared to 94.5 +/- 8.4% Harris Benedict (p = 0.05). REE declined by 3% during adjuvant chemotherapy (p < 0.05), and remained depressed until at least 3 months posttreatment. There were no significant changes in dietary intake or physical activity over the year. Failure of women to reduce their energy intake to compensate for the decreased energy requirement may account for some of the weight gain. Treatment of adjuvant chemotherapy causes gain of body fat because of reduced energy expenditure, and the failure of women to reduce their energy intake to compensate for the decline in energy requirement during and in the 6 months posttreatment. Since weight gain impacts on survival, patients should be counselled to reduce energy intake and exercise during and after adjuvant treatment.

Changes in body composition in men and women with advanced nonsmall cell lung cancer (NSCLC) undergoing chemotherapy.

BACKGROUND: Men with nonsmall cell lung cancer (NSCLC) are more susceptible to weight loss than women. The composition and aetiology of these gender specific weight changes are not known. METHODS: Measurements of body mass, body composition and energy balance (resting energy expenditure and energy intake) were made in 15 men and six women before and after chemotherapy for NSCLC. RESULTS: Over the course of chemotherapy minimal weight change was observed in both men and women. Men increased body fat from 25.0 +/- 5.5 to 27.9 +/- 7.9% (P < 0.05) whereas fat free mass (FFM) tended to decrease (P = 0.063). There was no change in body fat or FFM in the women. In the men resting energy expenditure decreased over the course of chemotherapy from 113.2 +/- 15.9 to 105.1 +/- 10.1% of the value predicted from the Harris Benedict equation (P < 0.05). In the women resting energy expenditure (REE) did not alter. CONCLUSION: Over the course of chemotherapy for NSCLC, men and women appear to have different patterns of change in body composition and in energy expenditure.

Acceptability and tolerance of a low tyrosine and phenylalanine diet in patients with advanced cancer -- a pilot study.

BACKGROUND: Low phenylalanine (phe) and tyrosine (tyr) diets limit tumour growth in animal models and may offer a novel cancer therapy. We studied the efficacy and acceptability of a low phe and tyr diet in patients with advanced cancer. METHODS: Patients with advanced metastatic melanoma (n=22) and metastatic breast cancer (n=15) were invited to follow a low phe and tyr diet (10 mg kg-1 phe and tyr per day) for 1 month. In those individuals who followed the diet for 1 month, we attempted to establish the effects on nutritional status (body weight, fat free mass, percentage body fat, serum albumin), immune cell function (white cell count, lymphocytes and neutrophils), plasma levels of phe-tyr and tryptophan and quality of life (Hospital Anxiety and Depression score). RESULTS: Only three of the 22 patients with metastatic melanoma and three of the 15 patients with metastatic breast cancer agreed to start the diet. All patients experienced problems and side-effects and increases in anxiety and depression. There were declines in weight, with loss of fat and fat free mass but slight increases in white cell counts and neutrophils. CONCLUSIONS: Low phe and tyr diets do not appear to be a viable treatment option for patients with advanced cancer.

Prediction of peak oxygen uptake in chronic fatigue syndrome.

OBJECTIVES: To establish a simple, valid, and acceptable method of predicting peak oxygen uptake (VO2peak) in patients with chronic fatigue syndrome (CFS), which could provide a basis for subsequent exercise prescription at an appropriate intensity as part of a clinical rehabilitation programme. METHODS: A total of 130 patients who met UK research criteria for CFS were taken from consecutive referrals for chronic fatigue to the University Department of Medicine at Withington Hospital, Manchester. VO2peak was determined using an incremental graded exercise test to exhaustion. Respiratory gas exchange, work rate, and heart rate were monitored throughout. RESULTS: In all patients, VO2peak was found to correlate strongly and significantly with peak work rate (WRpeak) during testing (r2 = 0.88, p<0.001). In patients who exercised for longer than two minutes (n = 119), regression analysis established the relation as Vo2peak = 13.1 x WRPpeak + 284, where VO2 is given in ml/min and WR in W. The mean error between the measured VO2peak and the predicted value was 10.7%. The relation between increase in work rate and oxygen uptake across the group was highly significant (r2 = 0.87, p<0.001), and given as VO2increase = 12.0 x WRincrease, this value being similar to that expected for healthy individuals. Almost all (97%) subjects reported no exacerbation of symptoms after maximal exercise testing. CONCLUSIONS: Using a simple to administer maximal exercise test on a cycle ergometer, it is possible to predict accurately the VO2peak of a patient with CFS from peak work rate alone. This value can then be used as an aid to setting appropriate exercise intensity for a rehabilitation programme. The increase in VO2 per unit increase in workload was consistent with that expected in healthy individuals, suggesting that the physiological response of the patients measured here was not abnormal. Contrary to the belief of many patients, maximal exercise testing to the point of subjective exhaustion proved to be harmless, with no subjects suffering any lasting deterioration in their condition after assessment.

The role of depression in pain, psychophysiological syndromes and medically unexplained symptoms associated with chronic fatigue syndrome.

BACKGROUND: The association between depression and pain, function, medically unexplained symptoms and psychophysiological syndromes such as irritable bowel syndrome has not been explored before in chronic fatigue syndrome. METHODS: Cross-sectional controlled study of the current prevalence of psychophysiological syndromes, pain, function and lifetime prevalence of medically unexplained symptoms in 77 out-patients with chronic fatigue syndrome (CFS) without DSM-III-R depression, 42 CFS out-patients with DSM-III-R depression and 26 out-patient with primary DSM-III-R depression. RESULTS: Both CFS groups differed significantly from the primary depression group but not each other in the prevalence of tension headaches (P < 0.001), reporting of widespread bodily pain (P < 0.001) and the number of lifetime medically unexplained symptoms (P < 0.001). The three groups did not significantly differ in the prevalence of irritable bowel syndrome or fibromyalgia. CFS patients with depression were more impaired in social function than other CFS patients. CONCLUSION: Depression is not associated with the reporting of pain, psychophysiological syndromes and medically unexplained symptoms in CFS patients. Depression is associated with decreased social function in CFS patients. LIMITATIONS: Study depended on recall of symptoms, not confirmed by medical records and current investigations. Patients with depression were taking antidepressants. CLINICAL RELEVANCE: Treating depression in chronic fatigue syndrome is unlikely to diminish reporting of pain and medically unexplained symptoms but may improve social function.

Randomised, double-blind, placebo-controlled treatment trial of fluoxetine and graded exercise for chronic fatigue syndrome.

BACKGROUND: The Joint Working Group of the Royal Colleges of Physicians, Psychiatrists and General Practitioners (1996) recommended graded exercise and antidepressants for patients with chronic fatigue syndrome. We assessed efficacy and acceptability of these treatments. METHOD: Six-month prospective randomised placebo and therapist contact time controlled trial with allocation to one of four treatment cells: exercise and 20 mg fluoxetine, exercise and placebo drug, appointments only and 20 mg fluoxetine, appointments and placebo drug. Drug treatment was double blind and patients were blind to assignment to exercise or appointments. RESULTS: Ninety-six (71%) of 136 patients completed the trial. Patients were more likely to drop out of exercise than non-exercise treatment (P = 0.05). In an intention to treat analysis, exercise resulted in fewer patients with case level fatigue than appointments only at 26 weeks (12 (18%) v. 4 (6%) respectively P = 0.025) and improvement in functional work capacity at 12 (P = 0.005) and 26 weeks (P = 0.03). Fluoxetine had a significant effect on depression at week 12 only (P = 0.04). Exercise significantly improved health perception (P = 0.012) and fatigue (P = 0.028) at 28 weeks. CONCLUSIONS: Graded exercise produced improvements in functional work capacity and fatigue, while fluoxetine improved depression only.

Energy and nitrogen balance and changes in midupper-arm circumference with multiple organ failure.

Energy intake and energy expenditure, nitrogen intake, and urinary nitrogen excretion (or urea production rates) were measured in 35 intravenously fed patients with multiple organ failure over the course of their illness to determine to what extent nutrient requirements were met despite fluid retention. Energy and nitrogen balance were related to serial measurements of midupper-arm circumference (MAC). The target feeding regimen of 176 kJ (42 kcal)/kg fat-free mass (FFM) was achieved in only three patients and the target of 0.24 g N/kg FFM in only four. Two patterns of change in MAC were noted: a steady decrease with time and no change with time. Serial muscle biopsy data indicated that all the patients were wasting away; the maintenance of MAC in the group with no change over time was due to fluid retention. Abnormal losses were not measured, but energy and nitrogen balance in the group in which arm circumference decreased had no apparent effect on the rate of wasting.

Fresh gas requirements of an enclosed afferent reservoir breathing system in anaesthetized, spontaneously breathing adults.

Using two methods of determining the onset of rebreathing, we have determined the minimum fresh gas flow rate (VF) of the Ohmeda enclosed afferent reservoir breathing system (EAR) in anaesthetized, spontaneously breathing adults. Rebreathing as defined by the Kain and Nunn criteria did not occur when the VF/VE ratio was greater than 0.70. A mathematical model was used to calculate the degree of rebreathing at each VF. From this model, rebreathing did not occur when VF was 0.86 VE or more and this value of VF/VE is considered appropriate to eliminate rebreathing in clinical practice.

Necrotizing myopathy in critically-ill patients.

Skeletal muscle wasting is commonly observed in critically-ill patients and has been attributed to catabolic fibre atrophy and to neuropathy. This study describes the occurrence of a necrotizing myopathy in 15 out of 31 critically-ill patients who had percutaneous biopsies taken from the tibialis anterior muscles. While most cases showed necrosis of isolated fibres, 5 of the 12 patients who had serial biopsies showed progressive necrosis of up to 95 per cent of the fibres. One other case showed infarction and one case had staphylococcal vasculitis. Atrophy of type 1 and/or type 2 fibres was documented by morphometry in 12 cases. Myoglobin-containing casts were demonstrated immunohistochemically in renal tubules on either biopsy or necropsy material in 5 out of 7 cases. The presence of muscle necrosis was a clinically unexpected finding which may contribute to weakness, complicate the interpretation of tissue biochemistry and energy balance studies, and potentiate renal failure. The necrosis is probably multifactorial in origin, with ischaemia and sepsis contributing factors.

Comparison of the metabolic effects of continuous postoperative enteral feeding and feeding at night only.

The effects of two different feeding patterns on oxygen consumption, nitrogen balance, blood biochemistry, and urinary catecholamine excretion were investigated over 5 d in patients after major head and neck surgery. Both groups of nine patients each were fed a regimen that provided 4.7 MJ on day 1 and 10 MJ on days 2-5 via a nasogastric tube by continuous infusion with an enteral feeding pump. One group was fed continuously for 24 h, the other was fed only at night, ie, from 1700 to 0900 the next morning. Oxygen consumption was significantly higher (P less than 0.01), nitrogen balance better (P less than 0.05), and urinary catecholamine excretion higher (P less than 0.05) in the 24-h-fed patients than in the night-fed patients. Postoperatively, feeding at night only is more energy efficient than is feeding continuously for 24 h, but is associated with poorer nitrogen balance. These differences may be mediated by sympathoadrenal mechanisms.

IV fluids during surgery.

During an attempt to measure renal function during operation in six patients undergoing major abdominal surgery involving intestinal resection and blood loss in excess of 300 ml, it became apparent that the conventional recommendation for i.v. crystalloid fluid of 5-10 ml kg-1 h-1 was not sufficient to maintain cardiovascular stability and urine output, but a volume of 15 ml kg-1 h-1, given to a subsequent six patients, was adequate. Administration of low sodium (glucose) solutions also produced biochemical abnormalities of a severity not documented previously. A survey of the published literature on volumes of crystalloid fluids used supports the contention that, during major surgery, crystalloid requirements may be of the order of 10-15 ml kg-1 h-1 rather than 5-10 ml kg-1 h-1.

Anaesthesia and acute dermatomyositis/polymyositis.

The anaesthetic management of two patients with severe muscle weakness--one suffering from acute dermatomyositis, the other from acute polymyositis--is described. Both patients presented for surgery for malignancy. Anaesthesia was induced with etomidate in one, thiopentone in the other. Alfentanil was used for analgesia and atracurium for muscle paralysis in both. Neuromuscular blockade was monitored using a peripheral nerve stimulator and no problems were experienced. Recovery of neuromuscular transmission and ventilatory function after operation were normal.

Arterial oxygenation after major head and neck surgery involving tracheotomy.

Changes in vital capacity, and in arterial PO2 and PCO2, were studies after major head and neck surgery involving tracheotomy and after surgery on the upper abdomen. After major head and neck surgery, changes in vital capacity were comparable to those seen after upper abdominal operations, with a decrease on day 1 of 39% recovering to 78% of the preoperative volume by day 7. Arterial PO2 in both groups decreased on day 1 but whereas PaO2 after upper abdominal surgery was recovering by day 7, PaO2 in the head and neck group, at day 7, showed no sign of recovery. Arterial PO2 7 days after major head and neck surgery was 2.3 (+/- 0.4) kPa below the preoperative value (P less than 0.001).

Thermoregulation, plasma catecholamine and metabolite levels during submaximal work in individuals susceptible to malignant hyperpyrexia.

Measurements of body temperature, respiratory gas exchange, sweat evaporation rate and circulating levels of catecholamines, lactate, pyruvate, free fatty acids and glucose were made in seven patients susceptible to malignant hyperpyrexia (MHS) and in seven control subjects during 2 h of treadmill walking at 40% of maximum oxygen consumption. These studies took place in an ambient temperature of 22 degrees C. The MHS patients displayed the same thermoregulatory, plasma catecholamine and metabolic responses as the control subjects. The results of the present study suggest that non-competitive, low-intensity, steady-state exercise need not be contraindicated for MHS patients.