The effect of catecholamines and adenosine deaminase on the glucose transport system in rat adipocytes.

2-Deoxyglucose uptake (3 min) and 3-O-methylglucose transport (2 s) was measured in rat adipocytes preincubated with 5 microM epinephrine plus adenosine deaminase as described by Green (Green, A. (1983) FEBS Lett. 152, 261-264). 2-Deoxyglucose uptake was about 95% depressed in insulin-treated, but not in 'basal', cells preincubated with epinephrine plus adenosine deaminase for 60 min in broad agreement with Green's report. However, this depression was caused by a decrease in sugar phosphorylation rather than transport. In similarly incubated cells, transport of 3-O-methylglucose, a sugar analogue not phosphorylated in the adipocytes, was not affected by catecholamine plus adenosine deaminase. However, a decrease in transport of about 60% was observed both in the absence and the presence of insulin when the albumin concentration was high enough and the cell concentration low enough to prevent accumulation of free fatty acids in the medium. In addition, the insulin sensitivity with regard to hexose transport was markedly reduced. Transport was approximately doubled in cells incubated with 5 microM epinephrine in the absence of adenosine deaminase. Thus, epinephrine at a high concentration stimulates hexose transport in the absence of adenosine deaminase (presence of adenosine) whereas it inhibits both basal and insulin-stimulated transport in the presence of adenosine deaminase (absence of adenosine).

IGF-I treatment in adults with type 1 diabetes: effects on glucose and protein metabolism in the fasting state and during a hyperinsulinemic-euglycemic amino acid clamp.

Type 1 diabetes is associated with abnormalities of the growth hormone (GH)-IGF-I axis. Such abnormalities include decreased circulating levels of IGF-I. We studied the effects of IGF-I therapy (40 microg x kg(-1) x day(-1)) on protein and glucose metabolism in adults with type 1 diabetes in a randomized placebo-controlled trial. A total of 12 subjects participated, and each subject was studied at baseline and after 7 days of treatment, both in the fasting state and during a hyperinsulinemic-euglycemic amino acid clamp. Protein and glucose metabolism were assessed using infusions of [1-13C]leucine and [6-6-2H2]glucose. IGF-I administration resulted in a 51% rise in circulating IGF-I levels (P < 0.005) and a 56% decrease in the mean overnight GH concentration (P < 0.05). After IGF-I treatment, a decrease in the overnight insulin requirement (0.26+/-0.07 vs. 0.17+/-0.06 U/kg, P < 0.05) and an increase in the glucose infusion requirement were observed during the hyperinsulinemic clamp (approximately 67%, P < 0.05). Basal glucose kinetics were unchanged, but an increase in insulin-stimulated peripheral glucose disposal was observed after IGF-I therapy (37+/-6 vs. 52+/-10 micromol x kg(-1) x min(-1), P < 0.05). IGF-I administration increased the basal metabolic clearance rate for leucine (approximately 28%, P < 0.05) and resulted in a net increase in leucine balance, both in the basal state and during the hyperinsulinemic amino acid clamp (-0.17+/-0.03 vs. -0.10+/-0.02, P < 0.01, and 0.25+/-0.08 vs. 0.40+/-0.06, P < 0.05, respectively). No changes in these variables were recorded in the subjects after administration of placebo. These findings demonstrated that IGF-I replacement resulted in significant alterations in glucose and protein metabolism in the basal and insulin-stimulated states. These effects were associated with increased insulin sensitivity, and they underline the major role of IGF-I in protein and glucose metabolism in type 1 diabetes.

The effect of recombinant human growth hormone on glucose and leucine metabolism in Cushing's syndrome.

Cushing's syndrome is characterized by central obesity and muscle wasting. As GH is anabolic, it may be able to counteract the loss of body protein. To evaluate the potential therapeutic use of GH preoperatively, eight patients with Cushing's syndrome received sc injections of recombinant human GH (0.07 U/kg.day) for 7 days. Whole body leucine and glucose turnover were measured after an infusion of [1-13C]leucine and [6,6-2H2]glucose before (day 0) and after 2 and 7 days of GH treatment. Compared with the value on day 0, there was a significant increase on days 2 and 7 in insulin (P < 0.005 and P < 0.001), C peptide (P < 0.01 and P < 0.005), insulin-like growth factor I (P < 0.001), and glucose concentrations (P < 0.01 and P < 0.005) and a decrease in the leucine concentration (P < 0.005). There was no significant change in glucose production rate, glucose MCR, leucine production rate (a measure of protein degradation), or nonoxidative leucine disappearance rate (a measure of protein synthesis). The leucine MCR was increased after 7 days (P < 0.05), and the clearance of leucine into protein (nonoxidative leucine disappearance rate/leucine concentration) was increased (P < 0.05) after 2 and 7 days of GH treatment. This is consistent with GH stimulating the availability of amino acid transporters. GH may, therefore, have a therapeutic role in the preoperative treatment of Cushing's syndrome.

Effect of growth hormone (GH) on glycerol and free fatty acid metabolism during exhaustive exercise in GH-deficient adults.

GH is an important regulator of fat metabolism at rest, but it is not known whether it regulates fat metabolism during exercise. To determine whether physiologic concentrations of GH influence fat metabolism during exercise, we randomized 16 GH-deficient adults, receiving long-term (mean duration, 5 yr) GH replacement, to either continue GH (n = 8) or receive identical placebo (n = 8) for a 3-month period. Metabolic studies, at rest, during and following exhaustive exercise were carried out at baseline and at the end of the 3 months. The rate of appearance of glycerol (glycerol Ra, an index of lipolysis) and free fatty acids (FFA, FFA Ra) and the rate of disappearance of FFA (FFA Rd) in the plasma were measured using infusions of (2)H(5)-glycerol and 1-(13)C-palmitic acid. Changes in body composition were assessed using dual-energy x-ray absorptiometry scanning and anthropometric measurements. In the baseline studies, exercise resulted in an increase in plasma glycerol and FFA concentrations, glycerol Ra, FFA Ra, and FFA Rd (P < 0.001). Three months of GH withdrawal resulted in reductions in plasma glycerol and FFA, glycerol Ra, FFA Ra, and FFA Rd at rest (P < 0.05 vs. baseline) and during exercise (P < 0.05 vs. baseline and vs. GH treated). Lean body mass decreased after 3 months of GH withdrawal, but total body fat, trunk fat, waist circumference, and the sum of skinfold thicknesses increased after 3 months of GH withdrawal (P < 0.05 vs. baseline and vs. GH treated). Fasting insulin and homeostasis model assessment of insulin resistance decreased after 3 months of GH withdrawal (P < 0.05 vs. baseline and vs. GH treated). In summary, GH withdrawal for 3 months resulted in reductions in release of glycerol and FFA into the circulation and uptake of FFA into the tissues during intense exercise. These changes were accompanied by reduced lean body mass and increased total body and trunk fat. Further studies are required to determine whether reduced mobilization of fat during exercise contributes to reduced exercise capacity and increased body fat in GH-deficient adults.

Expression of amyloid precursor protein in human astrocytes in vitro: isoform-specific increases following heat shock.

The beta-amyloid protein deposited in senile plaques and cerebral blood vessels in the Alzheimer's disease brain is derived from the larger transmembrane spanning amyloid precursor protein. The present study investigates the effects of heat shock on the expression and processing of amyloid precursor protein in a normal human fetal astrocytic cell line CC2565 using reverse transcription-polymerase chain reaction, in situ hybridization histochemistry and western blot analysis. Heat shock led to an increase in the messenger RNA encoding Kunitz protease inhibitor isoforms of amyloid precursor protein, which peaked at 4h post-heat shock. This increase was confined to the messenger RNA encoding amyloid precursor protein-751, with a decrease in amyloid precursor protein-770 and no change in amyloid precursor protein-695. This shift in splicing was accompanied by a significant decrease in secreted amyloid precursor protein and an increase in beta-secretase processing within the cell. These findings demonstrate that astrocytes in vitro demonstrate a striking response to heat shock. This is unlikely to be due to a direct action on the promoter region of the gene, since the response is specific for one splice variant; amyloid precursor protein-751 messenger RNA. This increase in expression is further accompanied by a decrease in secretion of amyloid precursor protein, implying a shift in processing towards an intracellular route, possibly via the actions of the beta-secretase enzyme, which is known to be potentially amyloidogenic. Such a mechanism may contribute to amyloidosis in the intact brain in response to cellular stress, such as head injury.

Effect of corticosterone on protein degradation in isolated rat soleus and extensor digitorum longus muscles.

The net catabolic effect of glucocorticoids on protein metabolism is well documented but the acute and chronic effect of glucocorticoids on protein breakdown remains controversial. In the present studies protein breakdown was measured by the release of tyrosine from the isolated soleus and extensor digitorum longus (EDL) muscles of control rats and rats treated with corticosterone (10 mg/100 g body weight/day) for 5 days. The effect of corticosterone in arresting growth was confirmed since corticosterone-treated rats weighed significantly less than control rats after 2, 3, 4 and 5 days of treatment (P < 0.001). Furthermore, the weights of soleus and EDL muscles from corticosterone-treated rats were significantly reduced (P < 0.001, at least P < 0.05 respectively) compared with muscles from control rats on days 3-5. In the EDL muscle tyrosine release was significantly elevated after corticosterone treatment for 2 days (257 +/- 21 nmol/g tissue/h, P < 0.05), 3 days (205 +/- 9 nmol/g tissue/h, P < 0.01), 4 days (255 +/- 20 nmol/g tissue/h, P < 0.005) and 5 days (218 +/- 8 nmol/g tissue/h, P < 0.05) compared with EDL from control rats (192 +/- 13, 171 +/- 7, 187 +/- 7, 180 +/- 12 nmol/g tissue/h respectively). In the soleus muscle, tyrosine release was significantly elevated after corticosterone treatment for 2 days (226 +/- 14 nmol/g tissue/h, P < 0.001), 3 days (223 +/- 16 nmol/g tissue/h, P < 0.001) and 4 days (199 +/- 10 nmol/g tissue/h, P < 0.001) compared with control rats (158 +/- 7, 132 +/- 6 and 153 +/- 7 nmol/g tissue/h respectively). After 5 days there was no significant difference in tyrosine release from soleus muscle between corticosterone-treated (176 +/- 15 nmol/g tissue/h) and control rats (157 +/- 6 nmol/g tissue/h). Plasma glucose concentrations were not significantly different in rats treated with corticosterone and control rats whilst insulin levels were significantly raised in the corticosterone-treated rats on all days compared with control rats (P < 0.05 on day 1; P < 0.001 on days 2, 3, 4 and 5). It is suggested that insulin may have prevented hyperglycaemia developing in the corticosterone-treated rats. Results from these studies indicate that the acute effect of glucocorticoids is to increase muscle proteolysis but this is not maintained with longer-term treatment.

Regional deposition of inhaled fog droplets: preliminary observations.

The regional deposition of a monodisperse 10-micron mass median aerodynamic diameter fog was studied in four healthy adult male nonsmokers. The fog was radiolabeled with technetium-99m sulfur colloid to enable detection by an Anger camera of deposited activity in the following regions of the respiratory tract: oropharynx, larynx, trachea, and intrapulmonary airways. Intrapulmonary deposition was further analyzed by computer with inner, intermediate, and outer zones, and within apical, intermediate and basal zones of the right lung. The radiolabeled aerosol was inhaled by mouth through a face-mask with the nasal airway occluded. Respiratory frequency, tidal volume, and jaw position were controlled and were commensurate with the oral component of oronasal breathing during moderate exercise. Deposition in the larynx, trachea, and intrapulmonary airways was a function of the scrubbing efficiency of the oropharynx, which differed substantially among subjects, and ranged from 72 to 99%. The density of the aerosol deposit in the larynx probably exceeded that of any of the subdivisions of the tracheobronchial tree and lung. Within the lung, deposition favored the inner zone (assumed to contain the larger airways) over the outer zone (assumed to be dominated by smaller airways and alveoli). Intrapulmonary aerosol distribution in an elderly subject with borderline evidence of airway obstruction differed from that observed in younger subjects. The possible consequences of altered lung elastic recoil, as may occur with aging, for regional dosimetry is discussed.

Exercise training reduces fatty acid availability and improves the insulin sensitivity of glucose metabolism.

AIMS/HYPOTHESIS: It is not known whether the beneficial effects of exercise training on insulin sensitivity are due to changes in hepatic and peripheral insulin sensitivity or whether the changes in insulin sensitivity can be explained by adaptive changes in fatty acid metabolism, changes in visceral fat or changes in liver and muscle triacylglycerol content. We investigated the effects of 6 weeks of supervised exercise in sedentary men on these variables. SUBJECTS AND METHODS: We randomised 17 sedentary overweight male subjects (age 50 +/- 2.6 years, BMI 27.6 +/- 0.5 kg/m(2)) to a 6-week exercise programme (n = 10) or control group (n = 7). The insulin sensitivity of palmitic acid production rate (Ra), glycerol Ra, endogenous glucose Ra (EGP), glucose uptake and glucose metabolic clearance rate were measured at 0 and 6 weeks with a two-step hyperinsulinaemic-euglycaemic clamp [step 1, 0.3 (low dose); step 2, 1.5 (high dose) mU kg(-1) min(-1)]. In the exercise group subjects were studied >72 h after the last training session. Liver and skeletal muscle triacylglycerol content was measured by magnetic resonance spectroscopy and visceral adipose tissue by cross-sectional computer tomography scanning. RESULTS: After 6 weeks, fasting glycerol, palmitic acid Ra (p = 0.003, p = 0.042) and NEFA concentration (p = 0.005) were decreased in the exercise group with no change in the control group. The effects of low-dose insulin on EGP and of high-dose insulin on glucose uptake and metabolic clearance rate were enhanced in the exercise group but not in the control group (p = 0.026; p = 0.007 and p = 0.04). There was no change in muscle triacylglycerol and liver fat in either group. CONCLUSIONS/INTERPRETATION: Decreased availability of circulating NEFA may contribute to the observed improvement in the insulin sensitivity of EGP and glucose uptake following 6 weeks of moderate exercise.

Noise exposure reduction aboard an oceangoing hopper dredge.

Reported industrial hygiene surveys aboard seagoing vessels are few, despite the presence of many potentially hazardous chemical and physical agents aboard ships. This investigation focused on crew noise exposure aboard an oceangoing hopper dredge. Noise exposure criteria were adopted based on the 24-hr equivalent continuous sound level (Leq(24)) because of the absence of standards for U.S. shipboard noise exposure. Personal noise dosimeters were used to measure the noise exposure of watchstanders, whose duties were predictable and repetitive. Watchstanders with high noise doses were asked to estimate their duration of exposure in specific areas of the vessel to enable calculation of noise dose per space. Noise sources within spaces associated with high noise dose were identified by sound pressure and surface vibration analysis in octave bands. Almost all accommodation spaces (cabins, recreation rooms, dining rooms, and hospital) were sufficiently quiet (sound pressure levels [SPLs] less than 65 dBA) to permit hearing threshold recovery. Machinery space SPLs ranged from 85 to 108 dBA, and engineering personnel noise exposure exceeded the selected criterion of Leq(24) = 80 dBA. Selective noise abatement and use of an enclosed operating station in the engine room were recommended to control engineering personnel noise exposure. This approach to noise exposure assessment and reduction should be applicable to other oceangoing ships where personnel may be exposed to noise 24 hr per day for weeks at a time.

The hepatic metabolism and biliary excretion of benzo[a]pyrene in guinea-pigs fed normal, high-fat or high-cholesterol diets.

Approx. one-third of an i.v. dose of 14C-benzo[a]pyrene was excreted within four hours in the bile of guinea-pigs fed a normal diet. The extent of excretion was not altered by feeding high-fat or high-cholesterol diets. Hepatic cytochromes P-450 and b5, and benzo[a]pyrene hydroxylase activity were unaltered by the administration of high-fat and high-cholesterol diets. Pretreatment with low oral doses of benzo[a]pyrene (6 X 3 mg/kg) did not induce these parameters in animals given any of the diets. High-fat and high-cholesterol diets altered the pattern of benzo[a]pyrene metabolites in the bile, with significantly increased excretion of dihydrodiol glucuronides in both the high-fat and high-cholesterol groups. Hepatic epoxide hydrolase activity and glutathione content were unaltered by the high-fat or high-cholesterol diets, and therefore cannot explain the alteration in the profile of biliary metabolites of benzo[a]pyrene. The altered pattern of biliary excretion in animals fed high-fat or high-cholesterol diets would lead to an increase in the delivery to the colon of dihydrodiol metabolites of benzo[a]pyrene.

The intestinal metabolism and DNA binding of benzo[a]pyrene in guinea-pigs fed normal, high-fat and high-cholesterol diets.

Strains of intestinal bacteria were capable of deconjugating benzo[a]pyrene metabolites in vitro. The hydrolysis products, and other primary oxidative metabolites of benzo[a]pyrene, were stable to further degradation by the strains tested. Cytochromes P-450 and b5 were detectable in the mucosa of the guinea-pig small intestine, but not in the mucosae of the colon or rectum. The concentrations were unaltered by administration of benzo[a]pyrene and/or the feeding of high-fat or high-cholesterol diets. Benzo[a]pyrene hydroxylase was measurable in the mucosa of the upper intestine, but was present in the lower gut only at very low levels in some animals. The activity was inducible, by oral administration of benzo[a]pyrene, in the small intestinal mucosa of guinea-pigs fed normal diet but not in those fed high-fat and high-cholesterol diets. Low levels of covalent binding of 3H to DNA of liver and gut mucosa were obtained in guinea-pigs dosed orally with 3H-benzo[a]pyrene. Comparison with data for animals given 3H2O suggested that approx. one quarter of the binding was probably due to 3H exchange during metabolism. The feeding of high-fat and high-cholesterol diets did not increase this binding. Guinea-pigs fed high-fat and high-cholesterol diets excreted a greater proportion of an oral dose of 3H-benzo[a]pyrene in urine, and less in faeces than animals fed a normal diet. Due to the low, and apparently non-inducible, levels of benzo[a]pyrene hydroxylase activity and of covalent binding in the colonic mucosa, the administration of benzo[a]pyrene to guinea-pigs fed high-fat or high-cholesterol diets appears unlikely to provide a novel animal model for studies on mechanisms of colon carcinogenesis.

The head dome: a simplified method for human exposures to inhaled air pollutants.

Acute controlled exposures of human subjects to air pollutants are customarily carried out with whole-body chambers, masks, or mouthpieces. The use of these methods may be limited by cost or technical considerations. To permit a study involving a highly unstable pollutant, artificial acid fog, administered to subjects during natural breathing, a head-only exposure chamber, called a head dome, was developed. It consists of a transparent cylinder with a neck seal which fits over the subject's head and rests lightly on his shoulders. The head dome does not constrain the upper airways or impede exercise on a bicycle ergometer. Ventilation can be monitored accurately and unobtrusively with a pneumotachograph at the exhaust port of the dome. A thermocouple may be used to monitor the onset and persistence of oronasal breathing. For short-term exposures to unstable or reactive pollutants lasting up to several hours, the head dome is an effective alternative to a whole-body chamber and probably superior to a face mask or mouthpiece.

Color preferences in films for fundus photography.

Photographs that provide a colorimetrically faithful image of the original object are known to be subjectively unacceptable. Color photographic films depict a distortion of the color of the original in order to produce a subjectively acceptable reproduction. The distorsions involved may not be appropriate for the reproduction of ocular fundus photographs. This paper assesses the performance of a variety of color slide films in producing photographs of the ocular fundus that are subjectively acceptable. Assessments were made of the photographs of the fundi of blond, dark Asian, and Indian patients. The result of the assessment is a recommendation that points toward the photographic film that will produce the subjectively most acceptable color reproduction.

Acute exposure to acid fog: influence of breathing pattern on effective dose.

Concern about the possible adverse health effects of acid fog has been fed by two observations: air pollution disasters earlier in this century were typically associated with fog, and current samples of fog water can be strongly acid. To study the acute effects of acid fog on the lung, the authors generated a monodisperse 10 microM MMAD aerosol of H2SO4 with a pH of 2.0 and a nominal concentration of 500 micrograms/m3. They exposed seven healthy young men on alternate days to acid or control equiosmolar NaCl aerosol during 40 min of resting ventilation and 20 min of exercise; the latter was sufficiently intense to induce oronasal breathing. Exposure was by means of a head dome, a head-only exposure device that permitted continuous measurement (unfettered breathing) of Vr, f, VE, and the onset and persistence of oronasal breathing. In this article the authors compare the relative importance of parameters contributing to the between-subject variability in estimated hydrogen ion dose to the lower airways (H+LAW), based on analysis of variance. Physiologic parameters accounted for 70% of the variability, of which 34% was due to differences in duration of oronasal breathing (tON) and 36% to differences in ventilation rate during oronasal breathing (VE(ON)); inhaled hydrogen ion concentration [H+], the environmental parameter, contributed only 30%. Minute ventilation at the time of transition from nasal to oronasal breathing varied significantly among subjects even if normalized to FVC, an index of lung size.

Response to acute ozone exposure in healthy men. Results of a screening procedure.

We screened 64 healthy, nonsmoking men, 18 to 35 yr old, for their sensitivity to 0.35 ppm ozone (O3) administered for 130 to 150 min with intermittent exercise. The changes in FVC, FEV1, AND FEF25-75 (p < 0.0001) immediately after O3 exposure varied widely among subjects. Histograms of the percentage changes in FVC and FEV1 did not differ from a unimodal, skewed (gamma) distribution (p = 0.99 and p = 0.17, respectively); the changes in FEF25-75 tended to deviate from a gamma distribution (p = 0.055). To adjust FEF25-75 for the confounding effects of O3 on FVC, we used multiple linear regression analysis with contemporaneous FVC as a covariable, analysis of a subgroup of nine subjects whose O3-induced FVC changes were < or = 5%, and volume correction of FEF25-75 for any changes in FVC after exposure. These analyses showed reductions in FEF25-75 unexplained by and following a different time course than the O3-induced changes in FVC. In 26 subjects also exposed to filtered air, significant effects of O3 on respiratory frequency (p < 0.004) and tidal volume (p < 0.0007) correlated weakly with FVC changes. The results confirm the wide variability in spirometric responsiveness among individuals to O3 and suggest that intrinsic narrowing of the small airways may be a significant component of the functional response.

Acute exposure to acid fog. Effects on mucociliary clearance.

Submicrometric sulfuric acid (H2SO4) aerosol can affect mucociliary clearance without eliciting irritative symptoms or changes in pulmonary function. The effect of larger fog droplets containing H2SO4 on mucociliary clearance is unknown. We quantified mucociliary clearance from the trachea (n = 4) and small airways (n = 7) of young healthy male adults after an acute exposure to H2SO4 fog (MMAD = 10.3 microns; pH = 2.0; liquid water content = 481 +/- 65 mg/m3; osmolarity = 30 mOsm). Acid fog (AF) or saline fog (SF) (10.9 microns; 492 +/- 116 mg/m3; 30 mOsm) was administered for 40 min of unencumbered breathing (no mouth-piece) at rest and for 20 min of exercise sufficient to produce oronasal breathing. Fog exposures were followed by a methacholine (MCh) challenge (a measure of airway reactivity) or inhalation of technetium-99M radioaerosol (MMAD = 3.4 microns) on 2 study days each. Changes in symptoms and forced ventilatory function were also assessed. Clearance was quantified from computer-assisted analyses of gamma camera images of the lower respiratory tract in terms of %removal/min of the radiolabel from the trachea 25 min after inhalation and from the outer zone of the right lung after 1.9 to 3 h. Symptoms, forced ventilatory function, and MCh response were unaffected by either fog. Tracheal clearance was more rapid in four of four subjects after AF (0.83 +/- 1.58% removal/min) compared with that after SF (-0.54 +/- 0.85% removal/min). Outer zone clearance was more rapid in six of seven subjects after AF (0.22 +/- 0.15% removal/min) compared with that after SF (0.01 +/- 0.09% removal/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Leucine metabolism in patients with Cushing's syndrome before and after successful treatment.

OBJECTIVE: Results from studies on the effect of glucocorticosteroids on protein turnover in both rat and man have been conflicting. The aim of this study was to investigate the primary cause of muscle wasting in patients with Cushing's syndrome. DESIGN: Studies of whole body 1(-14)C-leucine turnover in patients with Cushing's syndrome before and after successful treatment, and in control subjects. PATIENTS: Eleven patients with Cushing's syndrome before and after (n = 5) treatment and 11 control subjects. MEASUREMENTS: Whole body 1(-14)C-leucine turnover to determine leucine metabolic clearance rate, leucine production rate, leucine oxidation rate and leucine incorporation into protein. RESULTS: Plasma leucine concentration (mean +/- SEM 100 +/- 6 mumol/l), leucine metabolic clearance rate (9.97 +/- 0.11 mumol/min/kg), leucine turnover (0.98 +/- 0.11 mumol/min/kg) and leucine incorporation into protein (0.71 +/- 0.09 mumol/min/kg) were all significantly reduced in patients with Cushing's syndrome compared with control subjects (122 +/- 6 mumol/l, P < 0.05; 13.61 +/- 1.27 mumol/min/kg, P < 0.05; 1.65 +/- 0.12 mumol/min/kg, P < 0.05; 1.46 +/- 0.10 mumol/min/kg, P < 0.001, respectively). Leucine oxidation rate was similar in the patients with Cushing's syndrome and control subjects. When leucine metabolism was expressed in terms of lean body mass (LBM) in five patients with Cushing's syndrome and 11 control subjects, leucine MCR, leucine turnover and leucine oxidation were not significantly different in the two groups. However, leucine incorporation into protein was significantly reduced (P < 0.001) in the patients with Cushing's syndrome (1.07 +/- 0.20 mumol/min/kg LBM) compared with control subjects (1.95 +/- 0.11 mumol/min/kg LBM). CONCLUSION: We conclude from these studies that the muscle wasting associated with Cushing's syndrome is primarily due to a reduction in protein synthesis.

Gait on a shoestring: falls and foot separation in parkinsonism.

A novel device for monitoring gait, which can be used in confined spaces, is described. In addition to distance/time assessment of gait, it measures foot separation whilst walking. A field trial illustrates its potential in the investigation of falls.