Effects of caffeine on energy metabolism, heart rate, and methylxanthine metabolism in lean and obese women.

The magnitude of coffee-induced thermogenesis and the influence of coffee ingestion on substrate oxidation were investigated in 10 lean and 10 obese women, over two 24-h periods in a respiratory chamber. On one occasion the subjects consumed caffeinated coffee and on the other occasion, decaffeinated coffee. The magnitude of thermogenesis was smaller in obese (4.9 +/- 2.0%) than in lean subjects (7.6 +/- 1.3%). The thermogeneic response to caffeine was prolonged during the night in lean women only. The coffee-induced stimulation of energy expenditure was mediated by a concomitant increase in lipid and carbohydrate oxidation. During the next day, in postabsorptive basal conditions, the thermogenic effect of coffee had vanished, but a significant increase in lipid oxidation was observed in both groups. The magnitude of this effect was, however, blunted in obese women (lipid oxidation increased by 29 and 10% in lean and obese women, respectively). Caffeine increased urinary epinephrine excretion. Whereas urinary caffeine excretion was similar in both groups, obese women excreted more theobromine, theophylline, and paraxanthine than lean women. Despite the high levels of urinary methylxanthine excretion, thermogenesis and lipid oxidation were less stimulated in obese than in lean subjects.

Shrinking lung syndrome successfully treated with rituximab and cyclophosphamide.

Shrinking lung syndrome (SLS) is an uncommon feature of systemic lupus erythematosus (SLE) characterized by dyspnea, pleuritic chest pain, diaphragmatic elevation, restrictive ventilatory defect and reduced respiratory muscle strength as measured by volitional tests. We report the case of a 28-year-old woman with overlapping features of SLE and Sjögren syndrome who developed severe SLS while receiving corticosteroids and azathioprine for severe polyarthritis. She was treated with a combination of rituximab and cyclophosphamide, which led to a dramatic improvement in her clinical condition and respiratory function tests. The increase in vital capacity was one of the highest among 35 published cases of SLS. Thus, restoring a near-normal lung function is an achievable goal in SLS, and the use of rituximab, with or without concomitant cyclophosphamide, certainly deserves further study in this setting.

Magnetic resonance stress tagging in ischemic heart disease.

High-dose dobutamine magnetic resonance stress testing has been shown to be superior to dobutamine stress echocardiography for diagnosis of coronary artery disease (CAD). We determined the feasibility of quantitative myocardial tagging during low- and high-dose dobutamine stress and tested the ability of global systolic and diastolic quantitative parameters to identify patients with significant CAD. Twenty-five patients suspected of having significant CAD were examined with a standard high-dose dobutamine/atropine stress magnetic resonance protocol (1.5-T scanner, Philips). All patients underwent invasive coronary angiography as the standard of reference for the presence (n = 13) or absence (n = 12) of significant CAD. During low-dose dobutamine stress, systolic (circumferential shortening, systolic rotation, and systolic rotation velocity) and diastolic (velocity of circumferential lengthening and diastolic rotation velocity) parameters changed significantly in patients without CAD (all P < 0.05 vs. rest) but not in patients with CAD. Identification of patients without and with CAD during low-dose stress was possible using the diastolic parameter of "time to peak untwist." At high-dose stress, none of the global systolic or diastolic parameters showed the potential to identify the presence of significant CAD. With myocardial tagging, a quantitative analysis of systolic and diastolic function was feasible during low- and high-dose dobutamine stress. In our study, the diastolic parameter of time to peak untwist as assessed during low-dose dobutamine stress was the most promising global parameter for identification of patients with significant CAD. Thus quantitative myocardial tagging may become a tool that reduces the need for high-dose dobutamine stress.

Asthme a début tardif [Late-onset asthma].

Late-onset asthma is a common disease, with characteristics that differentiate it from childhood asthma persisting in adults, including a heterogeneity of underlying mechanism, a correlation with occupational exposure and the tendency to chronicize. Inadequate perception of the disease importance and difficulties in diagnosis, due to the association to COPD, the broad differential diagnosis spectrum and an atypical clinical manifestation, make this disease entity underdiagnosed and under-treated, with consequences for morbidity and mortality. The treatment of adults with asthma follows the usual guidelines, but must take into account an occasional poor therapeutic response and the risk of side effects in polymorbid patients.

Transfer factor for carbon monoxide: a glance behind the scene.

The transfer factor for carbon monoxide (TLCO) is widely used in pulmonary function laboratories because it represents a unique non-invasive window on pulmonary microcirculation. The TLCO is the product of two primary measurements, the alveolar volume (VA) and the CO transfer coefficient (KCO). This test is most informative when VA and KCO are examined, together with their product TLCO. In a normal lung, a low VA due to incomplete expansion is associated with an elevated KCO, resulting in a mildly reduced TLCO. Thus, in case of low VA, a seemingly "normal KCO" must be interpreted as an abnormal gas transfer. The most common clinical conditions associated with an abnormal TLCO are characterised by a limited number of patterns for VA and KCO: incomplete lung expansion, discrete loss of alveolar units, diffuse loss of alveolar units, emphysema, pulmonary vascular disorders, high pulmonary blood volume, alveolar haemorrhage.

Effect of inspiratory threshold loading on ventilatory kinetics during constant-load exercise.

Humoral factors play an important role in the control of exercise hyperpnea. The role of neuromechanical ventilatory factors, however, is still being investigated. We tested the hypothesis that the afferents of the thoracopulmonary system, and consequently of the neuromechanical ventilatory loop, have an influence on the kinetics of oxygen consumption (VO2), carbon dioxide output (VCO2), and ventilation (VE) during moderate intensity exercise. We did this by comparing the ventilatory time constants (tau) of exercise with and without an inspiratory load. Fourteen healthy, trained men (age 22.6 +/- 3.2 yr) performed a continuous incremental cycle exercise test to determine maximal oxygen uptake (VO2max = 55.2 +/- 5.8 ml x min(-1) x kg(-1)). On another day, after unloaded warm-up they performed randomized constant-load tests at 40% of their VO2max for 8 min, one with and the other without an inspiratory threshold load of 15 cmH2O. Ventilatory variables were obtained breath by breath. Phase 2 ventilatory kinetics (VO2, VCO2, and VE) could be described in all cases by a monoexponential function. The bootstrap method revealed small coefficients of variation for the model parameters, indicating an accurate determination for all parameters. Paired Student's t-tests showed that the addition of the inspiratory resistance significantly increased the tau during phase 2 of VO2 (43.1 +/- 8.6 vs. 60.9 +/- 14.1 s; P < 0.001), VCO2 (60.3 +/- 17.6 vs. 84.5 +/- 18.1 s; P < 0.001) and VE (59.4 +/- 16.1 vs. 85.9 +/- 17.1 s; P < 0.001). The average rise in tau was 41.3% for VO2, 40.1% for VCO2, and 44.6% for VE. The tau changes indicated that neuromechanical ventilatory factors play a role in the ventilatory response to moderate exercise.

Magnetic resonance cholangiography features of biliary abnormalities due to cavernous transformation of the portal vein.

BACKGROUND: The aim of this retrospective and monocentric study was to describe the magnetic resonance cholangiography (MRC) features of biliary abnormalities related to extrahepatic obstruction of the portal vein (EHOPV). METHODS: From September 2001 to May 2003, MRC was performed in 10 consecutive patients who had a portal thrombosis. RESULTS: Biliary ductal pathology was demonstrated via MRC in nine patients. It consisted of stenoses, ductal narrowing or irregularities involving the common bile duct for three patients with extrahepatic portal vein thrombosis discovered a mean of 1.5 years ago, or involving both right and left intrahepatic bile ducts and common bile duct for six patients with extrahepatic portal vein thrombosis discovered a mean of 16.2 years ago. Dilation of intrahepatic bile ducts was seen for seven patients, four of them having cholestasis. For three patients with symptomatic cholestasis, direct cholangiography (DC) was performed and showed the same findings as MRC which nevertheless overestimated the degree of bile duct stenosis. CONCLUSIONS: MRC seems to constitute an accurate tool to investigate noninvasively patients with portal biliopathy.

Closure of large intrathoracic airway defects using extrathoracic muscle flaps.

BACKGROUND: Prospective assessment of pedicled extrathoracic muscle flaps for the closure of large intrathoracic airway defects after noncircumferential resection in situations where an end-to-end reconstruction seemed risky (defects of > 4-cm length, desmoplastic reactions after previous infection or radiochemotherapy). METHODS: From 1996 to 2001, 13 intrathoracic muscle transpositions (6 latissimus dorsi and 7 serratus anterior muscle flaps) were performed to close defects of the intrathoracic airways after noncircumferential resection for tumor (n = 5), large tracheoesophageal fistula (n = 2), delayed tracheal injury (n = 1) and bronchopleural fistula (n = 5). In 2 patients, the extent of the tracheal defect required reinforcement of the reconstruction by use of a rib segment embedded into the muscle flap followed by temporary tracheal stenting. Patient follow-up was by clinical examination bronchoscopy and biopsy, pulmonary function tests, and dynamic virtual bronchoscopy by computed tomographic (CT) scan during inspiration and expiration. RESULTS: The airway defects ranged from 2 x 1 cm to 8 x 4 cm and involved up to 50% of the airway circumference. They were all successfully closed using muscle flaps with no mortality and all patients were extubated within 24 hours. Bronchoscopy revealed epithelialization of the reconstructions without dehiscence, stenosis, or recurrence of fistulas. The flow-volume loop was preserved in all patients and dynamic virtual bronchoscopy revealed no significant difference in the endoluminal cross surface areas of the airway between inspiration and expiration above (45 +/- 21 mm(2)), at the site (76 +/- 23 mm(2)) and below the reconstruction (65 +/- 40 mm(2)). CONCLUSIONS: Intrathoracic airway defects of up to 50% of the circumference may be repaired using extrathoracic muscle flaps when an end-to-end reconstruction is not feasible.

Hepatic Manifestations of Wilson Disease - CHUV Experience 2005-2010

Background and aim: Wilson disease (WD) is an inherited disorder ofhepatic copper excretion leading to toxic accumulation of copper in theliver as well as the brain, cornea, and other organs. The defect is due tomutations of the copper-transporting ATPase ATP7B. Here, we describethe adult cases of hepatic WD diagnosed at the CHUV between 2005and 2010.Methods: Clinical manifestions, results of diagnostic tests, and follow-upof adult patients with hepatic WD were recorded systematically.Results: Seven new adult cases of hepatic WD were diagnosed in ourcenter between 2005 and 2010. Three were women and 4 men, with amedian a ge at d iagnosis o f 24 (range, 1 8-56) years. Three patientspresented with acute liver failure (ALF), three with persistently elevatedliver function tests, and one with a dvanced cirrhosis. None hadneurological manifestations. Only one patient, presenting with ALF, had aKayser-Fleischer corneal ring. Median ceruloplasmin levels at diagnosiswere 0.13 (range, <0.03-0.30) g/l, median 24 h urinary copper excretion6.3 (range, 0.4-62.0) μmol/24 h, and median hepatic copperconcentration 591 (range, 284-1049) μg/g. At least one mutation in theATP7B g ene was i dentified in a ll patients. Allelic frequency of t hecommon H1069Q mutation was 14%. Two patients presenting with ALFand the one with advanced cirrhosis underwent successful l ivertransplantation. One patient with ALF recovered under chelator therapy.D-penicillamine was used as first-line chelator treatment, with a switch totrientine due to adverse effects in 2 out of 4 patients u nder l ong-termtreatment.Conclusions: The clinical presentation of WD and the performance ofdiagnostic tests are variable. A high index of suspicion i n clinicallycompatible situations i s key, with a combination of tests allowing thediagnosis of WD.

F+0 renography in neonates and infants younger than 6 months: an accurate method to diagnose severe obstructive uropathy.

We studied the response to F+0 renography and the relative and absolute individual kidney function in neonates and &lt; 6-mo-old infants before and after surgery for unilateral ureteropelvic junction obstruction (UJO). METHODS: The results obtained at diagnosis and after pyeloplasty for 9 children (8 boys, 1 girl; age range, 0.8-5.9 mo; mean age +/- SD, 2.4 +/- 1.5 mo) with proven unilateral UJO (i.e., affected kidney [AK]) and an unremarkable contralateral kidney (i.e., normal kidney [NK]) were evaluated and compared with a control group of 10 children (6 boys, 4 girls; age range, 0.8-2.8 mo; mean age, 1.5 +/- 0.7 mo) selected because of symmetric renal function, absence of vesicoureteral reflux or infection, and an initially dilated but not obstructed renal pelvis as proven by follow-up. Renography was performed for 20 min after injection of (123)I-hippuran (OIH) (0.5-1.0 MBq/kg) immediately followed by furosemide (1 mg/kg). The relative and absolute renal functions and the response to furosemide were measured on background-subtracted and depth-corrected renograms. The response to furosemide was quantified by an elimination index (EI), defined as the ratio of the 3- to 20-min activities: An EI &gt; or = 3 was considered definitively normal and an EI &lt; or = 1 definitively abnormal. If EI was equivocal (1 &lt; EI &lt; 3), the response to gravity-assisted drainage was used to differentiate AKs from NKs. Absolute separate renal function was measured by an accumulation index (AI), defined as the percentage of (123)I-OIH (%ID) extracted by the kidney 30-90 s after maximal cardiac activity. RESULTS: All AKs had definitively abnormal EIs at diagnosis (mean, 0.56 +/- 0.12) and were significantly lower than the EIs of the NKs (mean, 3.24 +/- 1.88) and of the 20 control kidneys (mean, 3.81 +/- 1.97; P &lt; 0.001). The EIs of the AKs significantly improved (mean, 2.81 +/- 0.64; P &lt; 0.05) after pyeloplasty. At diagnosis, the AIs of the AKs were significantly lower (mean, 6.31 +/- 2.33 %ID) than the AIs of the NKs (mean, 9.43 +/- 1.12 %ID) and of the control kidneys (mean, 9.05 +/- 1.17 %ID; P &lt; 0.05). The AIs of the AKs increased at follow-up (mean, 7.81 +/- 2.23 %ID) but remained lower than those of the NKs (mean, 10.75 +/- 1.35 %ID; P &lt; 0.05). CONCLUSION: In neonates and infants younger than 6 mo, (123)I-OIH renography with early furosemide injection (F+0) allowed us to reliably diagnose AKs and to determine if parenchymal function was normal or impaired and if it improved after surgery.

Traitement des fibroses pulmonaires idiopathiques [Treatment of idiopathic pulmonary fibrosis]

Idiopathic pulmonary fibrosis still has to be diagnosed by elimination. Neoplasm, toxic treatments, collagen vascular disease, professional exposure or diagnosis such as sarcoidosis have to be ruled out. The repercussions on gas exchange are the most reliable indications of the severity of the disease, the pulmonary function test or chest x-rays alone being often misleading. Transbronchic biopsies, thoracotomy or thoracoscopies provide a precise diagnosis. In many cases only broncho-alveolar lavage and a high resolution CT-scan are performed to rule out infection or tumor and to assess the inflammatory state of the disease. Due to the often poor prognosis of this disease and its often poor response to steroids, the role of cytostatic drugs, cyclosporine and colchicine, and of pulmonary graft is discussed.

Chronic subjective dizziness

CONCLUSION: Chronic subjective dizziness (CSD) is frequent and affects twice as many women as men. Anxiety is a strong predisposing factor. The pathophysiologic concept of this disorder assumes that balance function and emotion share common neurologic pathways, which might explain that the balance disorder can provoke fear and vice versa, giving rise to a problem in perception of space and motion. In anxious patients this can turn into a space and motion phobia, with avoidance behaviour. OBJECTIVE: CSD is a diagnosis based on the hypothesis of an interaction between the vestibular system and the psychiatric sphere. Patients complain of chronic imbalance, worsened by visual motion stimulation, and frequently suffer from anxiety. Vestibular examination reveals no anomalies. We evaluated the incidence and characteristics of CSD in patients referred to our neuro-otology centre (tertiary hospital outpatient clinic). SUBJECTS AND METHODS: This was a retrospective study of 1552 consecutive patients presenting with vertigo. CSD was diagnosed in 164 patients (female:male=111:53). RESULTS: CSD represents 10.6% of the dizzy patients in our clinic. Psychiatric disorder, mainly anxiety, was found in 79.3% of the cases. Other frequently associated factors were fear of heights and former vestibular lesion (healed). In all, 79.0% of the patients with CSD had poor balance performance on dynamic posturography testing.

Urea nitrogen, creatinine, and uric acid levels in postmortem serum, vitreous humor, and pericardial fluid.

Urea nitrogen, creatinine, and uric acid are relatively stable in postmortem serum and may, therefore, be used for diagnostic purposes when chronic kidney disease and end-stage renal failure are investigated as causes of death. Nevertheless, uncertainties remain in defining the best alternative to postmortem serum for the identification and assessment of significantly decreased kidney function. In this study, we investigated urea nitrogen, creatinine, and uric acid levels in postmortem serum, pericardial fluid, and vitreous humor in a series of medico-legal cases (500 autopsies) with various causes of death. No postmortem interval-related differences were observed in any of the investigated fluids for any analyzed parameter, confirming the biochemical stability of all compounds after death. Data analysis failed to reveal statistically significant differences between postmortem serum and pericardial fluid urea nitrogen, creatinine, and uric acid concentrations. Conversely, statistically significant differences were observed in all analyzed biomarkers between postmortem serum and vitreous humor levels, with lower concentrations of all markers measured in vitreous. The results of this study suggest that, in order to estimate as accurately as possible blood analyte concentrations at the time of death, pericardial fluid should be preferred to vitreous humor.

Hypersensitivity pneumonitis secondary to lovebirds: a new cause of bird fancier's disease.

Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease due to the repetitive inhalation of antigens. Most new cases arise from residential exposures, notably to birds, and are thus more difficult to recognise. The present authors report a 59-yr-old male who complained of dyspnoea and cough while being treated with amiodarone. Pulmonary function tests revealed restriction and obstruction with low diffusing lung capacity for carbon monoxide and partial pressure of oxygen. A high-resolution computed tomography chest scan and bronchoalveolar lavage showed diffuse bilateral ground-glass attenuation and lymphocytic alveolitis, respectively. Initial diagnosis was amiodarone pulmonary toxicity, but because of a rapidly favourable evolution, this diagnosis was questioned. A careful environmental history revealed a close contact with lovebirds shortly before the onset of symptoms. Precipitins were strongly positive against lovebird droppings, but were negative against other avian antigens. The patient was diagnosed with hypersensitivity pneumonitis to lovebirds. Avoidance of lovebirds and steroid treatment led to rapid improvement. The present observation identifies a new causative agent for hypersensitivity pneumonitis and highlights the importance of a thorough environmental history and of searching for precipitins against antigens directly extracted from the patient's environment. These two procedures should allow a more precise classification of some cases of pneumonitis, and thus might avoid progression of active undiagnosed hypersensitivity pneumonitis to irreversible fibrosis or emphysema.

Combined pulmonary fibrosis and emphysema syndrome in connective tissue disease.

OBJECTIVE: Connective tissue diseases (CTDs) are associated with several interstitial lung diseases. The aim of this study was to describe the recently individualized syndrome of combined pulmonary fibrosis and emphysema (CPFE) in a population of patients with CTD. METHODS: In this multicenter study, we retrospectively investigated data from patients with CTD who also have CPFE. The demographic characteristics of the patients, the results of pulmonary function testing, high-resolution computed tomography, lung biopsy, and treatment, and the outcomes of the patients were analyzed. RESULTS: Data from 34 patients with CTD who were followed up for a mean±SD duration of 8.3±7.0 years were analyzed. Eighteen of the patients had rheumatoid arthritis (RA), 10 had systemic sclerosis (SSc), 4 had mixed or overlap CTD, and 2 had other CTDs. The mean±SD age of the patients was 57±11 years, 23 were men, and 30 were current or former smokers. High-resolution computed tomography revealed emphysema of the upper lung zones and pulmonary fibrosis of the lower zones in all patients, and all patients exhibited dyspnea during exercise. Moderately impaired pulmonary function test results and markedly reduced carbon monoxide transfer capacity were observed. Five patients with SSc exhibited pulmonary hypertension. Four patients died during followup. Patients with CTD and CPFE were significantly younger than an historical control group of patients with idiopathic CPFE and more frequently were female. In addition, patients with CTD and CPFE had higher lung volumes, lower diffusion capacity, higher pulmonary pressures, and more frequently were male than those with CTD and lung fibrosis without emphysema. CONCLUSION: CPFE warrants inclusion as a novel, distinct pulmonary manifestation within the spectrum of CTD-associated lung diseases in smokers or former smokers, especially in patients with RA or SSc.