New data on efficacy of valacyclovir in secondary prevention of maternal-fetal transmission of cytomegalovirus.

OBJECTIVE: Congenital cytomegalovirus (CMV) infection is the leading cause of non-genetic hearing and neurological deficits. The aim of our study was to evaluate the efficacy and safety of valacyclovir (VCV) treatment in preventing CMV transmission to the fetus after maternal primary infection. METHODS: This was a retrospective, multicenter study evaluating the rate of maternal-fetal CMV transmission in pregnancies with maternal primary CMV infection treated with VCV at a dosage of 8 g per day (VCV group) compared with a control group of untreated women. Each case underwent virological testing to confirm maternal primary infection and to provide accurate dating of onset of infection. The primary outcome was the presence of congenital CMV infection at birth diagnosed based on polymerase chain reaction analysis of saliva, urine and/or blood samples. The efficacy of VCV treatment was assessed using logistic regression analysis adjusted for a propensity score. RESULTS: In total, 143 patients were included in the final analysis, of whom 59 were in the VCV group and 84 were in the untreated control group. On propensity-score-adjusted analysis, VCV treatment was significantly associated with an overall reduction in the rate of maternal-fetal CMV transmission (odds ratio, 0.40 (95% CI, 0.18-0.90); P = 0.029). The rate of maternal-fetal CMV transmission, determined at birth, in the VCV vs control group was 7% (1/14) vs 10% (1/10) after periconceptional maternal primary infection (P = 1.00), 22% (8/36) vs 41% (19/46) after first-trimester maternal primary infection (P = 0.068) and 25% (2/8) vs 52% (14/27) after second-trimester maternal primary infection (P = 0.244). When analyzing the efficacy of VCV treatment according to maternal viremia at treatment initiation, there was a trend towards greater efficacy when patients were viremia-positive (21% vs 43%; P = 0.072) compared with when they were viremia-negative (22% vs 17%; P = 0.659). Maternal side effects associated with VCV were mild and non-specific in most cases. CONCLUSION: Our findings indicate that VCV treatment of pregnant women with primary CMV infection reduces the risk of maternal-fetal transmission of CMV and may be effective in cases with primary infection in the first and second trimesters. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

[Management of HPV-induced cervical lesions in immunosuppressed patients - Review of the literature]. / Prise en charge des lésions cervicales HPV induites chez les patientes immunodéprimées ­ Revue de la littérature.

INTRODUCTION: Current French recommendations for the management of cervical lesions related to human papilloma virus (HPV) infection are limited to general population. Patients who are immunocompromised appear to be at increased risk of induced HPV lesions. The objective of this review is to summarize the various existing data about risk of induced HPV lesions in immunocompromised patients to specify the management. METHODS: The Medline database was searched through the Pubmed portal, as well as the recommendations of various international learned societies. RESULTS: Situations with an increased risk are regardless of treatment: Human Immunodeficiency Virus (HIV) infection, transplants, lupus. Patients with chronic inflammatory bowel disease (IBD) and rheumatoid arthritis are at increased risk only when immunosuppressive therapy is required. Screening for dysplasic intraepithelial lesions in HIV+ patients should be more sustained than in the general population. Due to lack of data, recommendations for other conditions have been extrapolated from the management of HIV+ patients. HPV vaccination is effective in these populations, particularly at times when the immune system is the most effective. DISCUSSION: Identified immunocompromised populations are at higher risk of induced HPV lesions due to an incomplete immune response and should be screened on a sustained basis. In addition, HPV vaccination should be encouraged.

Causes and consequences of fever during pregnancy: A retrospective study in a gynaecological emergency department.

OBJECTIVE: Fever is a very common reason for emergency consultation during pregnancy, and may be associated with maternal, obstetrical and/or fetal adverse outcomes. The aim of this study was to determine the etiologies and to analyze the maternal or fetal complications of fever in pregnancy. STUDY DESIGN: A retrospective single center study including all patients who consulted for fever above 38 °C during pregnancy in the gynecological emergency ward from August 2016 to July 2017. RESULTS: A total of 100 pregnant women who consulted for fever were included. The etiologies were common viral infections (37 %), influenza (21 %), pyelonephritis (11 %), viral gastroenteritis (6%), chorioamnionitis (5%), other (5%). The etiology was unknown for 15 %. Fever was confirmed during consultation in 45/100 patients (45 %). Among patients with confirmed fever, 21/45 (47 %) were hospitalized with a median stay of 3 days [IQR 2-4] and 10/45(22 %) developed fetal or maternal complications. Probabilistic antibiotics were delivered for 34/45, 76 % patients. Only 14/45, 31 % had confirmed bacterial infections. Of the 32 patients with confirmed fever who had no etiologic diagnosis at the initial work-up in the emergency room, 19/32, 59 % received presumptive treatment with amoxicillin against Listeria monocytogenes. None had confirmed listeriosis, and all were probably common viral infections. Among all patients, the complications rate was 13 % and 22 % in the subgroup with fever confirmed at presentation. CONCLUSIONS: This study quantifies the main etiologies and complications of fever during pregnancy. A challenge is to reduce excessive antibiotic use by improving rapid diagnosis of bacterial and viral infections. Prospective studies are needed to target patients at risk of complications in an optimal way and to study new management strategies.

Prenatal description of retinal coloboma.

Retinal coloboma is a rare condition which is difficult to diagnose in foetuses. It can cause blindness. It can be isolated or associated with other malformations in various syndromes. Our objective is to describe the different prenatal ultrasound findings and management of coloboma. We describe a case of prenatal ultrasound diagnosis of retinal coloboma at 27.5 weeks of gestation. Our case adds to the 8 previously reported in the prenatal ultrasound literature, which together illustrate that microphthalmia is the main associated sign, present in 66.6% (6/9) of cases followed by retro-orbital cysts (44.4%) (4/9). These two ultrasound findings should alert us to a close examination of the eye to look for a posterior retinal cleft, the main direct sign of a chorioretinal coloboma.

Dose-response relationship between ambulatory load magnitude and load-induced changes in COMP in young healthy adults.

OBJECTIVE: To determine the dose-response relationship between ambulatory load magnitude during a walking stress test and load-induced changes in serum concentration of cartilage oligomeric matrix protein (sCOMP) in healthy subjects. DESIGN: sCOMP was assessed before and after a 30-min walking stress test performed on three test days by 24 healthy volunteers. In each walking stress test, one of three ambulatory loads was applied in a block randomized crossover design: normal body weight (BW) (100%BW = normal load); reduced BW (80%BW = reduced load); increased BW (120%BW = increased load). Knee kinematics and ground reaction force (GRF) were measured using an inertial sensor gait analysis system and a pressure plate embedded in the treadmill. RESULTS: Load-induced increases in sCOMP rose with increasing ambulatory load magnitude. Mean sCOMP levels increased immediately after the walking stress test by 26.8 ± 12.8%, 28.0 ± 13.3% and 37.3 ± 18.3% for the reduced, normal or increased load condition, respectively. Lower extremity kinematics did not differ between conditions. CONCLUSIONS: The results of this study provide important evidence of a dose-response relationship between ambulatory load magnitude and load-induced changes in sCOMP. Our data suggests that in normal weight persons sCOMP levels are more sensitive to increased than to reduced load. The experimental framework presented here may form the basis for studying the relevance of the dose-response relationship between ambulatory load magnitude and load-induced changes in biomarkers involved in metabolism of healthy articular cartilage and after injury.

Effects of prolonged exposure to CO2 on behaviour, hormone secretion and respiratory muscles in young female rats.

Atmospheric CO2 concentrations increased significantly over the last century and continuing increases are expected to have significant effects on current ecosystems. This study evaluated the behavioural and physiological (hormone status, muscle structure) effects of prolonged CO2 exposure in young female Wistar rats exposed at 700ppm of CO2 during 6h a day for 15days. Prolonged CO2 exposure, though not continuous, produced significant disturbances in behaviour with an increase in drinking, grooming and resting, and a reduction in rearing, jumping-play and locomotor activity. Furthermore, CO2 exposure was accompanied by increased plasma levels of corticosterone, suggesting that prolonged exposure to CO2 was stressful. The muscular structure can also be modified also when respiratory working conditions change. The expression of myosin heavy chain was significantly affected in the diaphragm and oral respiratory muscles: Masseter Superficialis and Anterior Digastric. Modified behaviour and hormonal changes both appear to be at the origin of the observed muscular adaptation.

Plasmablastic lymphoma: oral presentation in patient suffering from osteradionecrosis of the jaw.

INTRODUCTION: We describe here an unusual presentation of a plasmablastic lymphoma in a patient suffering from an osteoradionecrosis of the jaw. PRESENTATION OF CASE: We report the case of a 64-year-old patient who was followed up on oncology because of an oropharyngeal cancer treated by a combined procedure of both surgery and radio-chemotherapy procedure. This patient developed an osteoradionecrosis of the jaw. In the vicinity of this necrotic area appeared an ulceration which could evoke a new necrotic area. Given the persistence of this ulceration, a biopsy was performed which highlighted a plasmablastic lymphoma oral localization. DISCUSSION: The plasmablastic lymphoma, belonging to the diffuse large B-cell lymphoma family, is a very aggressive and unusual form of cancer with poor prognosis. If it is found mainly in patients with positive HIV, in whom it was first described, it is also found in immunosuppressed patients such as transplanted patients or patients suffering from leukaemia. CONCLUSION: Plasmablastic lymphoma is a rare and an aggressive pathology in immunocompetent patients.

Joint instability leads to long-term alterations to knee synovium and osteoarthritis in a rabbit model.

OBJECTIVES: Joint instability is believed to promote early osteoarthritic changes in the knee. Inflammatory reactions are associated with cartilage degradation in osteoarthritis (OA) but their possible synergistic or additive effects remain largely unexplored. The goal of the present study was to investigate the in vivo effects of Botulinum Toxin A (BTX-A) induced joint instability on intraarticular alterations in an otherwise intact rabbit knee joint model. METHODS: Ten 1-year-old female New Zealand White rabbits (average 5.7 kg, range 4.8-6.6 kg) were randomly assigned to receive three monthly unilateral intramuscular injections of BTX-A (experimental group), or no treatment (control group). After 90 days, all knees were analyzed for specific mRNA levels using RT-qPCR. The synovium and cartilage tissue was assessed for histological alterations using the OARSI scoring system. RESULTS: Cartilage and synovial histology showed significant higher OARSI scores in the BTX-A group animals compared to the untreated controls and contralateral limbs. There were no differences between the untreated control and the contralateral experimental limbs. Gene expression showed significant elevations for collagen I, collagen III, nitric oxide, TGF-ß, IL-1 and IL-6 compared to the healthy controls. CONCLUSION: BTX-A induced joint instability in a muscle weakness model uniquely leads to alterations in gene expression and histological changes in the synovial membranes and cartilage in otherwise intact knee joints. These results lead to the conclusion that joint instability may promote an inflammatory intraarticular milieu, thereby contributing to the development of OA.

Doppler sonographic examination of uterine and placental perfusion in cows in the last month of gestation and effects of epidural anesthesia and isoxsuprine.

The massive increase in size of the fetus and uterus in the last trimester is accompanied by an increasing demand for nutrients and oxygen, and it is assumed that this demand is met by increasing uterine and fetal perfusion. The goals of this study were to measure the perfusion of the uterine arteries and the placentomes in the last month of gestation and to investigate the effect of epidural anesthesia and isoxsuprine on perfusion. During the last month of gestation, eight Braunvieh cows underwent nine color Doppler sonographic examinations of the uterine arteries to determine diameter (DM), pulse rate (PR), resistance index, time-averaged maximum blood flow velocity (TAMV), and blood flow volume (BFV), and power-mode Doppler sonography was used to determine perfusion of placentomes. The PR increased (P < 0.001), and the BFV and TAMV of the ipsilateral uterine artery decreased between 4.5 and 0.5 weeks prepartum (BFV, 236.8 ± 65.80 and 208 ± 41.52 cm(3)/s, P < 0.01; TAMV, 140.0 ± 26.53 cm/s and 125.2 ± 18.46 cm/s, P < 0.05). After sonographic examination, the cows received epidural administration of local anesthetic (100-mg lidocaine) in the sacrococcygeal space or isoxsuprine (200 mg/cow, iv), and the sonographic measurements were repeated 30 minutes later. After epidural anesthesia, the TAMV and BFV of the contralateral uterine artery increased by 5.4% (P < 0.05) and 7.9% (P < 0.01). In the placentomes of the gravid uterine horn, the relative placentome perfusion and the color pixel grading (Cp) increased by 10.1% (P < 0.05) and 11.5% (P < 0.01) after epidural anesthesia. After isoxsuprine, the DM, PR, and BFV increased by 4.7%, 49.3%, and 16.9% in the ipsilateral uterine artery and by 10.8%, 48.7%, and 22.8%, respectively in the contralateral uterine artery. The TAMV of the ipsilateral uterine artery increased by 7.1% (P < 0.01), and the resistance index decreased in both uterine arteries (ipsilateral 24.2%, contralateral 14.9%, both P < 0.00001). Isoxsuprine increased the relative placentome perfusion and the Cp of the placentomes by 18.1% and 18.3% in the gravid horn and by 10.2% and 24.2% in the nongravid horn. Blood flow variables changed little in the last month of gestation. However, epidural anesthesia and isoxsuprine caused changes in uterine and placentome perfusion that suggest improvement of placental nutrient and oxygen supply to the fetus.

Effect of muscle weakness and joint inflammation on the onset and progression of osteoarthritis in the rabbit knee.

OBJECTIVES: Interactions between mechanical and non-mechanical independent risk factors for the onset and progression of Osteoarthritis (OA) are poorly understood. Therefore, the goal of the present study was to investigate the in vivo effects of muscle weakness, joint inflammation and the combination on the onset and progression of OA in a rabbit knee joint model. MATERIALS AND METHODS: Thirty 1-year-old female New Zealand White rabbits (average 5.7 kg, range 4.8-6.6 kg) were divided into four groups with one limb randomly assigned to be the experimental side: (1) surgical denervation of the vastus lateralis (VL) muscle; (2) muscle weakness induced by intramuscular injection of Botulinum toxin A (BTX-A); (3) intraarticular injection with Carrageenan to induce a transient inflammatory reaction; (4) combination of Carrageenan and BTX-A injection. After 90 days, cartilage histology of the articular surfaces were microscopically analyzed using the Osteoarthritis Research Society International (OARSI) histology scoring system. RESULTS: VL denervation resulted in significantly higher OARSI scores in the patellofemoral joint (group 1). BTX-A administration resulted in significant cartilage damage in all four compartments of the knee (group 2). Carrageenan did not cause significant cartilage damage. BTX-A combined with Carrageenan lead to severe cartilage damage in all four compartments. CONCLUSION: Muscle weakness lead to significant OA in the rabbit knee. A transient local inflammatory stimulus did not promote cartilage degradation nor did it enhance OA progression when combined with muscle weakness. These results are surprising and add to the literature the conclusion that acute inflammation is probably not an independent risk factor for OA in this rabbit model.

Bio-specific and bio-orthogonal chemistries to switch-off the quencher of a FRET-based fluorescent probe: application to living-cell biothiol imaging.

We report the first molecular system that is responsive to both a bio-specific and a bio-orthogonal stimulus. This dual activation process was applied to the design of a biothiol-specific FRET-based fluorescent probe that could be turned-on via an original concept of quencher bleaching.

[Pyometra and persistent hymen in an alpaca]. / Pyometra mit persistierendem Hymen bei einem Alpaka.

A 3-year-old female alpaca was referred to the hospital because of tenesmus. Clinical examination revealed a habitual vaginal prolapse with tenesmus during urination and defecation. On vaginoscopic examination a persistent hymen was detected. Ultrasonography of the caudal abdomen showed an echogenic fluid-filled uterus. A diagnostic laparotomy led to diagnosis of pyometra. Following ovariohysterectomy, the recovery was uneventful. One and a half years later the alpaca was again admitted to the hospital because of colic. Based on the findings, a tentative prognosis was provided and the alpaca was euthanized at the request of the owner. At necropsy, a haemorrhagic infarction of a jejunal loop was found due to incarceration in a fibrous adhesion between the vaginal stump and small intestine.

[Results after osteosynthesis of extraarticular proximal phalangeal fractures]. / Ergebnisse osteosynthetisch versorgter Grundphalanxfrakturen der Finger.

The aim of the study was to retrospectively present and analyse the functional results of surgically treated extraarticular fractures of the proximal phalanx.From 1/2005-4/2008 we operated on 49 patients with 52 closed, extraarticular fractures of the proximal phalanx of the long fingers with either pins, screws or plates. 30 patients were male, 19 were female, the mean age was 35 years. Open fractures, fractures of the thumb and those with injuries to neurovascular structures or tendons were excluded. Postoperative physiotherapy was started on day 1 after surgery. Postoperative finger function and complications were analysed based on the total active motion (TAM) regarding the Belsky score and the classification of Page and Stern. In addition, patients were contacted by phone in 4/2009 to verify the subjective functional results at the end of the observation period.Three different operative procedures were employed: internal fixation by Kirschner wires (n=25), and open fixation by screws (n=8) or plates (n=19). The entire treatment period amounted to 12 (4-28) weeks, the observation time was 33 (11-50) months. Two patients, both after plate osteosynthesis, had to be reoperated because of functional deficits due to adhesions. In both a tenolysis and removal of the plate was performed. The functional result was excellent in 20 of 25 patients treated by Kirschner wires, in seven of the eight in the screw-fixation group and in 13 of the 19 patients treated by plate ostheosynthesis (TAM > 240°); the result was judged fair in 1 after plate osteosynthesis (TAM 215°). The remaining 11 patients showed a good outcome with a TAM between 220° and 239°. These favourable results remained subjectively stable at the end of the observation period, when all patients could be contacted by phone.Osteosynthesis by kirschner wires, screws and plates for closed extraarticular fractures of the proximal phalanx of the long fingers gives good to excellent results with few complications.

A nondestructive method for obtaining maternal DNA from avian eggshells and its application to embryonic viability determination in herring gulls (Larus argentatus).

Many avian studies, aimed at collecting samples for genetic analysis, rely upon invasive procedures involving the capture and handling of parents and their offspring. Our goal was to develop a nondestructive method for sampling maternal DNA that would not require blood collection from the mother. Herein, we describe a method for isolating genomic DNA from eggshell powder, obtained by filing the outer shell of an avian egg. Comparison of microsatellite profiles, obtained from genomic DNA found within eggshell matrices and their corresponding parents, verified the presence of maternal DNA in the eggshell matrix in 100% of the herring gull nests assessed (n= 11). In addition, the microsatellite profiles of eggshell DNA were identical among eggs from the same clutch. The ability to rapidly obtain a DNA sample from an avian eggshell in a noninvasive manner could aid in a wide range of genetic sampling studies, and in this study, we provide one potential application of this finding: assessing the fertilization status of nonviable herring gull (Larus argentatus) eggs from the Laurentian Great Lakes. Detection of fertilization was successful as the microsatellite profiles of eggshell powder (maternal only) and the fertilized embryonic contents of those eggs did not match. Ideally, the application of such an approach will help to discriminate unfertilized eggs from embryos aborted early in development and provide insights into avian reproductive health.

Intraocular pressure lowering efficacy of travoprost.

PURPOSE: To assess the intraocular pressure lowering effect of travoprost 0.004% in patients previously treated with another topical medication, and in previously untreated patients. METHODS: This 12-week, open-label trial in 1590 patients was conducted at 219 sites in Switzerland. Primary open-angle glaucoma and ocular hypertension patients discontinued prior medications, and instilled 1 drop of travoprost in each affected eye at 8 pm. Untreated patients were subdivided into 2 groups: baseline IOP of > or = 21 mmHg, and baseline IOP of < or = 20 mmHg. Patients returned for follow-up visits at 1 and 3 months. The primary outcome was mean IOP change from baseline to follow-up. RESULTS: Of 626 patients previously on monotherapy, and 525 previously untreated or newly-diagnosed patients, 479 and 423, respectively, completed 3 months of therapy. The mean changes from baseline at 1 month (mmHg +/- SD), by prior treatment group were: beta blocker, -4.9 (+/- 3.6); latanoprost, -2.3 (+/- 2.8); alpha-agonist, -4.0 (+/- 3.7); dorzolamide/timolol fixed combination, -3.4 (+/- 3.9); topical CAI, -4.4 (+/- 3.1); new IOP > or = 21 mmHg, -8.6 (+/- 4.4); new IOP < or = 20 mmHg, -4.4 (+/- 3.0). (All changes from baseline were statistically significant (p < 0.0001). CONCLUSIONS: In patients previously treated with a single drug, travoprost decreased IOP to pressures below those achieved on prior therapy. In all groups, travoprost reduced mean IOP below 18 mmHg within 1 month of starting therapy, and control was maintained for at least 3 months. Overall, travoprost was safe and well-tolerated.

Early reduction in plasma norepinephrine during beta-blocking therapy with metoprolol in chronic heart failure.

BACKGROUND: The possible role exerted by modulation of sympathetic outflow in the clinical effects of beta-blockade in chronic heart failure was tested during short- and long-term treatment. METHODS AND RESULTS: Oral metoprolol (30-150 mg/day) was added to conventional therapy in 14 patients with idiopathic dilated cardiomyopathy, left ventricular ejection fraction (LVEF) of <0.45, and New York Heart Association class II or III. Norepinephrine plasma levels, which are an index of sympathetic activation, decreased by 27.57 +/- 18.03% after 1 month (P < .005), but returned to pretreatment levels after 6 months. LVEF increased by 7.7 +/- 6.0 ejection fraction units after 6 months (P < .005 vs baseline and P < .05 vs 1 month). Long-term beta-blockade resulted in nonsignificant improvements in functional class, symptom score, and oxygen consumption at peak exercise. After 1 month, the reduction in plasma norepinephrine levels and the changes in LVEF were inversely correlated (P < .01). No other correlation emerged during short- or long-term treatment. CONCLUSION: In conclusion, the reduction in plasma norepinephrine levels during short-term beta-blockade was not proportional to the clinical benefits and may have been attributed to the direct inhibition of sympathetic outflow. The early reduction in circulating norepinephrine levels may decrease cardiac performance through withdrawal of sympathetic support when the favorable effects of beta-blockade have not had time to occur. The role that sympathetic modulation may exert in the long-term clinical benefits of metoprolol deserves further investigation.

Myocardial dysfunction and abnormal left ventricular exercise response in autonomic diabetic patients.

In diabetic patients, the pathophysiologic mechanisms of exercise-induced left ventricular (LV) dysfunction remain controversial. In this study, the role of myocardial contractility recruitment in determining an abnormal LV response to isometric or dynamic exercise has been investigated in 14 diabetic patients with autonomic dysfunction. Ischemic heart disease was excluded by the absence of LV wall motion abnormalities induced by isotonic and isometric exercise and by coronary angiography. Left ventricular and myocardial function were studied at rest, and during isometric and isotonic exercise, by two-dimensional echocardiography; moreover, recruitment of an inotropic reserve was assessed by postextrasystolic potentiation at rest and at peak handgrip. An abnormal response of LV ejection fraction to isometric (9/14) or to dynamic (8/14) exercise was frequent in study patients. In these patients, baseline myocardial contractility was normal, and the significant increase in ejection fraction by postextrasystolic potentiation indicated a normal contractile reserve (65 +/- 7% vs. 74 +/- 6%, p = 0.001). Nevertheless, the downward displacement of LV ejection fraction-systolic wall stress relationships during exercise suggests an inadequate increase in myocardial contractility. However, the abnormal ejection fraction at peak handgrip was completely reversed by postextrasystolic potentiation (67 +/- 6% vs. 58.1 +/- 10%, p = 0.008), a potent inotropic stimulation independent of the integrity of adrenergic cardiac receptors. A defective inotropic recruitment, despite the presence of a normal LV contractile reserve, plays an important role in deexercise LV dysfunction in diabetic patients with autonomic neuropathy.

Influence of beta-blockade with metoprolol on symptoms and functional capacity of patients with idiopathic dilated cardiomyopathy.

Long-term treatment with beta-adrenergic blocking drugs has been shown to induce clinical amelioration in patients with chronic heart failure. However, the efficacy of these agents has not been consistent, and the mechanisms of their beneficial effects remain to be established. The present study evaluated the influence of oral metoprolol on symptoms and exercise tolerance of patients with idiopathic dilated cardiomyopathy (3 women and 9 men, left ventricular ejection fraction < 0.45, NYHA functional class II or III). One patient did not tolerate metoprolol, whereas 11 patients terminated the study. After 6 months of beta-blocking therapy, detectable improvements of symptoms (NYHA class and questionnaire-derived symptom score) were observed in 6 patients. Six patients reported an increase in functional capacity [oxygen consumption at peak exercise (VO2p) during cardiopulmonary exercise test]. For the whole group, no significant changes in symptoms and exercise tolerance were detected. During exercise, oxygen pulse (VO2/heart rate) and VO2/RPP (VO2/heart rate/systolic pressure) were significantly increased after 6 months on metoprolol (+35, 9% and +27.1%, respectively; both p < 0.01 vs baseline). In conclusion, beta-blocking therapy was well tolerated by the majority of patients, some of which reported improvement of symptoms and functional capacity. The observed increase on oxygen pulse and Vo2/RPP suggests that beta-blockade may reduce myocardial oxygen requirements in proportion to cardiac work. An increase in the energy available to myocardial cells for synthetic and reparative processes may thus account, at least in part, for the beneficial influence of long-term beta-blockade in heart failure patients.