Evolution of Salmonella spp. isolated compared to those of Campylobacter spp. in faecal samples for 12 years.

OBJECTIVE: The Autonomous Community of Galicia has adopted DECREE 216/2011 on health standards for poultry production, in addition to the Spanish national programs. However, no program has yet been implemented to eradicate campylobacteriosis, which shares the same reservoir. The aim of this study was to compare the evolution of Salmonella spp. isolates with respect to those of Campylobacter spp. in faecal samples received by the Microbiology Department. METHODS: A retrospective descriptive comparative study was conducted through the Laboratory Information System (SIL) of Salmonella spp. isolated against Campylobacter spp. in faeces between 2011 and 2022 at the Lucus Augusti University Hospital (HULA), Lugo, Spain. RESULTS: A total of 35,704 stool samples were analysed, of which 3,045 were positive. 751 Salmonella spp. were isolated. Statistical differences were observed in the annual distribution (p<0.01), with a clear turning point in 2018. Five hundred and five patients required hospital care, especially in 2014 with 72 patients (69%). On the other hand, 1,587 Campylobacter spp. were isolated. Required hospital care 1,002 patients during the study, with a peak in 2019 with 111 cases (62%). CONCLUSIONS: The reduction of salmonellosis cases and the maintenance of campylobacteriosis cases are directly related to the implementation of DECREE 216/2011. This, in turn, has reduced the pressure on hospitals in the HULA health area. Therefore, we believe that the ONE Health concept is being strengthened in the area studied.

Long-term (≥15 years) Follow-up of Percutaneous Coronary Intervention of Unprotected Left Main (From the GRAVITY Registry).

Long term survival and its determinants after Percutaneous Coronary Intervention (PCI) on Unprotected Left Main Coronary Artery (ULMCA) remain to be appraised. In 9 European Centers 470 consecutive patients performing PCI on ULMCA between 2002 and 2005 were retrospectively enrolled. Survival from all cause and cardiovascular (CV) death were the primary end points, while their predictors at multivariate analysis the secondary ones. Among the overall cohort 81.5% of patients were male and mean age was 66 ± 12 years. After 15 years (IQR 13 to 16), 223 patients (47%) died, 81 (17.2%) due to CV etiology. At multivariable analysis, older age (HR 1.06, 95%CI 1.02 to 1.11), LVEF < 35% (HR 2.97, 95%CI 1.24 to 7.15) and number of vessels treated during the index PCI (HR 1.75, 95%CI 1.12 to 2.72) were related to all-cause mortality, while only LVEF <35% (HR 4.71, 95%CI 1.90 to 11.66) to CV death. Repeated PCI on ULMCA occurred in 91 (28%) patients during the course of follow up and did not significantly impact on freedom from all-cause or CV mortality. In conclusion, in a large, unselected population treated with PCI on ULMCA, 47% died after 15 years, 17% due to CV causes. Age, number of vessels treated during index PCI and depressed LVEF increased risk of all cause death, while re-PCI on ULMCA did not impact survival.

Effects of policosanol in the functional recovery of non-cardioembolic ischemic stroke hypertensive patients. / Efectos del policosanol en la recuperacion funcional de pacientes hipertensos con ictus isquemico no cardioembolico.

INTRODUCTION: Clinical studies results show that policosanol (20 mg/day) + aspirin therapy had benefits versus placebo + aspirin to patients with recent non-cardioembolic ischemic stroke. AIM: To analyze the policosanol treatment effects in the hypertensive patients included in two non-cardioembolic ischemic stroke recovery trials. PATIENTS AND METHODS: Hypertensive patients with a modified Rankin Scale (mRS) score 2 to 4 were randomized, within 30 days of onset, to policosanol + aspirin or placebo + aspirin, for six months. The primary outcome was mRS score reduction. RESULTS: One hundred forty two hypertensive patients (mean age: 66 years) were included in the analysis. Policosanol + aspirin decreased significantly the mRS score mean from the first interim check-up. The policosanol treatment effect did not wear off, on the contrary, even improved after six months therapy. More over, policosanol + aspirin (80.3%) treatment achieved significant results (mRS <= 1), whereas the placebo + aspirin did not (8.5%). Two patients discontinued and four (two from each group) referred mild adverse events. CONCLUSIONS: The treatment for six months with policosanol + aspirin in hypertensive patients who had suffered a non-cardioembolic ischemic stroke proved to be more effective than the placebo + aspirin treatment in the functional recovery of these patients.

TITLE: Efectos del policosanol en la recuperacion funcional de pacientes hipertensos con ictus isquemico no cardioembolico.Introduccion. Los resultados de los estudios clinicos muestran que el tratamiento con policosanol (20 mg/dia) + aspirina produce beneficios frente a placebo + aspirina en pacientes con ictus isquemico no cardioembolico reciente. Objetivo. Analizar los efectos del tratamiento con policosanol en pacientes hipertensos incluidos en dos ensayos de recuperacion de ictus isquemico no cardioembolico. Pacientes y metodos. Pacientes hipertensos que sufrieron un ictus en los 30 dias previos y que, con una puntuacion de 2 a 4 en la escala de Rankin modificada (mRS), se distribuyeron aleatoriamente en dos grupos y recibieron policosanol + aspirina o placebo + aspirina durante seis meses. La variable primaria de eficacia fue la reduccion de la puntuacion en la mRS. Resultados. Se incluyo a un total de 142 pacientes hipertensos (edad media: 66 años) en el analisis. El policosanol + aspirina disminuyo significativamente la puntuacion de la mRS desde el primer chequeo intermedio. El efecto del tratamiento con policosanol no desaparecio, sino que incluso mejoro despues de seis meses de tratamiento. El numero de pacientes que alcanzaron valores de la mRS <= 1 fue mayor en el grupo de policosanol + aspirina (80,3%) que en el de placebo + aspirina (8,5%). Dos pacientes causaron baja del estudio y cuatro (dos de cada grupo) refirieron efectos adversos leves. Conclusiones. El tratamiento durante seis meses con policosanol + aspirina a pacientes hipertensos que habian sufrido un ictus isquemico no cardioembolico demostro ser mas efectivo que el tratamiento con placebo + aspirina en su recuperacion funcional.

Nintedanib for the treatment of patients with refractory metastatic colorectal cancer (LUME-Colon 1): a phase III, international, randomized, placebo-controlled study.

Background: Angiogenesis is critical to colorectal cancer (CRC) growth and metastasis. Phase I/II studies have demonstrated the efficacy of nintedanib, a triple angiokinase inhibitor, in patients with metastatic CRC. This global, randomized, phase III study investigated the efficacy and safety of nintedanib in patients with refractory CRC after failure of standard therapies. Patients and methods: Eligible patients (Eastern Cooperative Oncology Group performance status 0-1, with histologically/cytologically confirmed metastatic/locally advanced CRC adenocarcinoma unamenable to surgery and/or radiotherapy) were randomized 1 : 1 to receive nintedanib (200 mg twice daily) or placebo (twice daily), until disease progression or undue toxicity. Patients were stratified by previous regorafenib, time from onset of metastatic disease to randomization, and region. Co-primary end points were overall survival (OS) and progression-free survival (PFS) by central review. Secondary end points included objective tumor response and disease control by central review. Results: From October 2014 to January 2016, 768 patients were randomized; 765 were treated (nintedanib n = 384; placebo n = 381). Median follow-up was 13.4 months (interquartile range 11.1-15.7). OS was not improved [median OS 6.4 months with nintedanib versus 6.0 months with placebo; hazard ratio (HR), 1.01; 95% confidence interval (CI), 0.86-1.19; P = 0.8659]. There was a significant but modest increase in PFS with nintedanib versus placebo (median PFS 1.5 versus 1.4 months, respectively; HR 0.58; 95% CI 0.49-0.69; P < 0.0001). There were no complete or partial responses. Adverse events (AEs) occurred in 97% of 384 nintedanib-treated patients and 93% of 381 placebo-treated patients. The most frequent grade ≥3 AEs were liver-related AEs (nintedanib 16%; placebo 8%) and fatigue (nintedanib 9%; placebo 6%). Conclusions: The study failed to meet both co-primary end points. Nintedanib did not improve OS and was associated with a significant but modest increase in PFS versus placebo. Nintedanib was well tolerated. ClinicalTrials.gov number: NCT02149108 (LUME-Colon 1).

Fast assessment of bioaccessible metallic contamination in marine sediments.

A fast (16min) procedure to assess the bioaccessible metallic fraction of Cd, Cr, Cu, Ni, Pb and Zn simultaneously extracted (SEM) from marine sediments plus an indirect approach to determine acid volatile sulfides (AVS) are presented. For the extraction process magnetic agitation was compared with ultrasonic stirring (using a bath and a probe), and several stirring times were assayed. The proposed SEM procedure uses an ultrasonic probe and 1mL of HCl. It dramatically minimizes the turnaround time and the residues. AVS were evaluated as the difference between the amounts of sulphur in the solid residue after the extraction and total sulphur in the original sample. These procedures are fast, easy to implement and cost-effective to assess the potential risk posed by metals in marine sediments. They were tested using several CRMs and applied to sediments from two Galician Rias (NW Spain); their SEM-AVS differences indicated no biological risk.

Mehran contrast nephropathy risk score: Is it still useful 10 years later?

BACKGROUND: Nowadays, contrast-induced nephropathy (CIN) is the third cause of acquired acute renal impairment in hospital. CIN is related to increased in-hospital morbidity, mortality, costs of medical care, and long admissions. Because of this, we hypothesized it would be useful to determine the risk of CIN with scores such as the Mehran score. The aim of this study was to validate the Mehran score in a contemporary cohort of Spanish patients with acute coronary syndrome (ACS). METHODS: We assessed the calibration and discriminatory capacity of Mehran score to predict CIN in a cohort of 1520 patients with a definitive diagnosis of ACS and who underwent coronary angiography between March 2008 and June 2012. We excluded patients on chronic dialysis and those without data of contrast volume. The calibration of the model was assessed with the Hosmer-Lemeshow goodness-of-fit test and discriminatory capacity was assessed by C-statistic, which is equivalent to the area under the receiver-operating characteristic curve. RESULTS: From the total group, 118 patients (7.8%) developed CIN. They were older, with higher rates of diabetes (DM) and hypertension and worse renal function and anemia (p<0.001). The odds ratios for different score components in Mehran's population versus our study were similar except for DM, hypotension, and intra-aortic balloon pump (1.6%, 2.68%, 2.55% vs 0.9%, 1.89%, and 2.86%, respectively). Calibration and discriminatory capacity of Mehran score were excellent with a Hosmer-Lemeshow p=0.7, C-statistic value >0.8. CONCLUSIONS: Mehran risk score has been validated in our study as a good score for predicting CIN in patients with ACS who underwent coronary angiography. According to this, we support its use in patients hospitalized for ACS in order to identify the ones at risk, and to optimize CIN prophylactic therapy prior to and after catheterization.

Impact of surveillance of hepatitis b and hepatitis c in patients with inflammatory bowel disease under anti-TNF therapies: multicenter prospective observational study (REPENTINA 3).

AIMS: Assess IBD patients starting anti-TNF for the impact of preventive measures in HBV and/or HCV, and the predictive response factors to HBV vaccination. METHODS: Multicenter prospective study including 389 IBD patients. Four interventions were established: I-1) anti-HBs <100IU/L: HBV vaccination with double doses at 0-1-2months, and revaccination if titres <100IU/L (seroprotection defined as anti-HBs10-100IU/L and effective vaccination anti-HBs >100IU/L); I-2) anti-HBs >100IU/L (previous effective vaccination): monitoring levels; I-3) anti-HBc and/or HCV+: analysis every two months; I-4) HBsAg+: start anti-virals. RESULTS: I-1 and I-2) For first vaccination, effective vaccination and seroprotection were obtained in 26.4% and 43.5%, and for revaccination 31.3% and 44.4%, respectively. Predictive factors of effective vaccination were age ≤30years (OR=2.2) and being vaccinated simultaneously with anti-TNF (OR=5.2) instead of late vaccination, whereas age ≤30years (OR=2.6) and anti-TNF monotherapy (OR=2.4) were predictive for seroprotection. 80.8% of patients previously vaccinated maintained titres at 29months follow-up. The only factor related to maintaining titres was previous vaccination versus achieving effective vaccination during anti-TNF (HR=2.49); I-3 and I-4) HBV-DNA + without reactivation was detected in 7% of 29 anti-HBc. No reactivation was found in the remaining HCV (n=5) or HBsAg (n=4) patients. CONCLUSIONS: 1) Response to vaccination/revaccination is low in patients with anti-TNF. Young patients vaccinated at the beginning of anti-TNF and receiving it as a monotheraphy showed better response. 2) Long-lasting effective vaccination is greatest in patients previously vaccinated. 3) Following-up the established surveillance and/or preventive anti-viral therapy seems to be safe in HBV and HCV patients.

Interpolation in the standard additions method.

The standard additions method (SAM) has traditionally been performed by using extrapolation. This practice is suboptimal because predictions are affected by even slight departures of calibration points from a straight line. Despite this, most textbooks and papers in analytical chemistry still refer exclusively to extrapolation. In contrast, the use of interpolation is recommended in this paper as a way to get predictions on the central part of the regression line and thus minimize the bias in the prediction and the variance associated with the analytical result. Several scenarios were studied, with concentration errors simulated in different calibration solutions. It was found that translational effects due to variations at the central part of the calibration caused the lowest disturbances on the predicted concentrations. The differences between the interpolated and extrapolated predictions can be as large as ±30%. The confidence interval associated with the extrapolation result is wider than that due to interpolation by as much as 100%. It is shown that commonly used equations underestimate the correct confidence intervals. Both, absence of bias and improved precision, are of relevance in quality assurance, method validation and error propagation.

Pancreatic fusocellular sarcoma. The importance of endoscopic ultrasound-guided fine needle aspiration in the differential diagnosis of solid pancreatic tumors.

In the presence of a pancreatic tumor, the main diagnostic problem is to determine the benign o malignant nature of the lesion, and then to evaluate its resectability. A preoperative biopsy was usually rejected based on the fact that negative results do not exclude malignancy, that such biopsy may hamper the possibility of curative surgery because of potential seeding along the biopsy s trajectory, that surgical morbidity and mortality are low, and also because of the high diagnostic sensitivity of the various imaging techniques. Biopsy for solid pancreatic tumors was limited to irresectable tumors, and isolated cases with suspicion of tuberculosis, lymphoma or neuroendocrine tumors. Nowadays the performance of a pancreatic biopsy is becoming essential for the correct management of solid lesions, and is useful not only to establish malignancy, but also for a better knowledge of all kind of pathologies and, thus, for better therapeutic management. In this context, endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) has proven a safe technique with a low rate of complications and a diagnostic accuracy superior to other procedures, this being considered the method of choice for the study of solid pancreatic lesions. An illustrative example is the case we report in this article -a patient diagnosed of a solid, locally advanced-stage pancreatic tumor with imaging techniques (abdominal ultrasounds and EUS) under EUS-guided FNA; the procedure could establish a final diagnosis of pancreatic fusocellular sarcoma.

Sarcoma fusocelular de páncreas: importancia de la PAAF guiada por ultrasonografía endoscópica en el diagnóstico diferencial de los tumores sólidos pancreáticos / Pancreatic fusocellular sarcoma. The importance of endoscopic ultrasound-guided fine needle aspiration in the differential diagnosis of solid pancreatic tumors

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Fiberoptic bronchoscopy in allogeneic bone marrow transplantation: findings in the era of serum cytomegalovirus antigen surveillance.

STUDY OBJECTIVES: Pulmonary complications occur in half of allogeneic bone marrow transplantation (BMT) patients. The incidence of these complications has been reduced by prophylaxis against Pneumocystis carinii pneumonia, preemptive therapy in patients at high risk for cytomegalovirus (CMV) reactivation, and, more recently, screening for serum CMV antigen. Since fiberoptic bronchoscopy (FOB) has historically been the primary diagnostic test to evaluate BMT patients with pulmonary disease, a review was performed to determine the impact, if any, that current prophylaxis and screening policies may have had on FOB utility. DESIGN: The records of 174 adult patients undergoing BMT between January 1997 and December 1999 were reviewed to determine the diagnostic yield of FOB and the frequency by which FOB altered management. RESULTS: Sixty-one patients underwent 76 bronchoscopies. FOB was diagnostic in 32 patients (42.1% of cases) and directly changed management in 24 patients (31.6% of cases). Half of these changes included the withdrawal of an antimicrobial agent. The most common findings were infection (32 cases) and diffuse alveolar hemorrhage (6 cases). CMV was the most prevalent infection identified, but FOB resulted in the addition of antiviral therapy to only two patients. P carinii pneumonia was not diagnosed in any patient studied. CONCLUSIONS: These data suggest a changing spectrum of pulmonary disease in BMT patients. FOB has limited impact on the diagnoses of CMV disease or P carinii pneumonia with current prophylaxis and screening strategies. It may be useful in identifying other infectious etiologies and in eliminating unnecessary antimicrobials.

Modulation of N-type Ca2+ channel current kinetics by PMA in rat sympathetic neurons.

The protein kinase C activator phorbol 12-myristate 13-acetate (PMA) has been used extensively in studies of G protein modulation of Ca2+ channels. PMA has been shown to be a powerful tool for inducing phosphorylation and interrupting G-protein-mediated signaling pathways. Here we re-examine the effects of PMA on whole-cell N-type Ca2+-channel currents in rat sympathetic neurons. We found that, along with an increase in the current amplitude previously reported by others, PMA pretreatment leads to alterations in current activation and inactivation kinetics. These alterations in current kinetics are voltage-dependent and are not reproduced by internal dialysis with the G protein inhibitor GDPbetaS. Alterations in current kinetics by PMA may therefore indicate the existence of a modulated state, presumably phosphorylated, of N-type Ca2+ channels. We propose that the increase in current amplitude is due primarily to alterations in current kinetics rather than to removal of tonic inhibition.

A long-term study of policosanol in the treatment of intermittent claudication.

Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects. This study was undertaken to investigate the long-term effects of policosanol administered to patients with moderately severe intermittent claudication. The study consisted of a 6-week single-blind, placebo-controlled run in phase, followed by a 2-year double-blind, randomized treatment step. Fifty-six patients who met study entry criteria were randomized to receive placebo or policosanol 10 mg twice daily. Walking distances on a treadmill (constant speed 3.2 km/h, slope 10 degrees, temperature 25 degrees C) were assessed before and after 6, 12, 18, and 24 months of treatment. Both groups were similar at randomization. After 6 months of therapy, policosanol significantly increased (p < 0.01) the initial claudication distance from 125.9 +/- 8.7 m to 201.1 +/- 24.8 m and the absolute claudication distance from 219.5 +/- 14.1 m to 380.7 +/- 50.2 m. Both variables remained unchanged in the placebo group (p < 0.01). These effects did not wear off but improved after long-term therapy, so that final values were 333.5 +/- 28.6 m (initial claudication distance) and 648.9 +/- 54.1 m (absolute claudication distance); both significantly greater (p < 0.0001) than those obtained in the placebo group, which showed values of 137.9 +/- 21.8 m (initial claudication distance) and 237.7 +/- 28.1 m (absolute claudication distance), respectively. At study completion, 21 policosanol and 5 placebo patients attained increases in claudication distance values > 50% (p < 0.001). Policosanol, but not placebo, significantly increased the ankle/arm pressure index. In addition, from month 6 up to study completion, the frequency of patients reporting improvement of lower limb symptoms was greater in the policosanol group than in the placebo group. The treatment was tolerated well. There were 16 withdrawals (12 placebo, 4 policosanol) from the study. Eight patients in the placebo group experienced a total of 10 serious adverse events, 8 of which were vascular events, compared with none in the policosanol group (p < 0.01). In addition, 3 patients in the policosanol group and 3 patients in the placebo group reported mild adverse events during the study. The present results demonstrate the long-term usefulness of policosanol therapy to treat patients with intermittent claudication.

Potentiation of prolactin secretion following lactotrope escape from dopamine action. I. Dopamine withdrawal augments l-type calcium current.

Hypothalamic dopamine (DA) tonically inhibits prolactin (PRL) release from the anterior pituitary gland. Transient escapes from this DA tone elicit a pronounced potentiation of the PRL-releasing action of secretagogues such as thyrotropin-releasing hormone (TRH). Previous evidence has suggested that modulation of Ca(2+) channels can be involved in this potentiation. With a lactotropic cell line (GH(4)C(1)) expressing human D(2)-DA receptors, we tested the hypothesis that a brief escape from the tonic inhibitory action of DA triggers a facilitation of Ca(2+) influx through Ca(2+) channels. We initially found that in these cells, DA effectively and reversibly inhibited PRL secretion, and reversibly enhanced an inwardly rectifying K(+) current. The effects of DA administration and withdrawal on Ca(2+) currents were examined using the patch-clamp technique in the whole-cell configuration and Ba(2+) as a divalent charge carrier through Ca(2+) channels. Macroscopic Ba(2+) currents were significantly decreased by short term (1-10 min) applications of DA (500 nM), which further declined following 24 h of constant exposure to DA. After DA removal, a biphasic facilitation of the density of Ba(2+) currents was observed. An initial 2-fold enhancement of conductance was detected between 10 and 40 min, followed by a second facilitation of the same magnitude observed 24 h after DA withdrawal. The present results directly demonstrate that dissociation of DA from D(2)-receptors expressed in GH(4)C(1) lactotrope cells causes an increase of high-voltage-activated Ca(2+) channel function, which may play an important role in the cross-talking amplification of endocrine cascades such as that involved in the TRH-induced PRL-release potentiating action of DA withdrawal.

G-protein beta-subunit specificity in the fast membrane-delimited inhibition of Ca2+ channels.

We investigated which subtypes of G-protein beta subunits participate in voltage-dependent modulation of N-type calcium channels. Calcium currents were recorded from cultured rat superior cervical ganglion neurons injected intranuclearly with DNA encoding five different G-protein beta subunits. Gbeta1 and Gbeta2 strongly mimicked the fast voltage-dependent inhibition of calcium channels produced by many G-protein-coupled receptors. The Gbeta5 subunit produced much weaker effects than Gbeta1 and Gbeta2, whereas Gbeta3 and Gbeta4 were nearly inactive in these electrophysiological studies. The specificity implied by these results was confirmed and extended using the yeast two-hybrid system to test for protein-protein interactions. Here, Gbeta1 or Gbeta2 coupled to the GAL4-activation domain interacted strongly with a channel sequence corresponding to the intracellular loop connecting domains I and II of a alpha1 subunit of the class B calcium channel fused to the GAL4 DNA-binding domain. In this assay, the Gbeta5 subunit interacted weakly, and Gbeta3 and Gbeta4 failed to interact. Together, these results suggest that Gbeta1 and/or Gbeta2 subunits account for most of the voltage-dependent inhibition of N-type calcium channels and that the linker between domains I and II of the calcium channel alpha1 subunit is a principal receptor for this inhibition.

Effect of policosanol on arterial blood pressure in rats. Study of the pharmacological interaction with nifedipine and propranolol.

BACKGROUND: Policosanol is a natural mixture of higher aliphatic primary alcohols isolated from sugar cane wax (Saccharum officinarum, L) with cholesterol-lowering effects demonstrated in experimental models and in patients with type II hyperlipoproteinemia. The purpose of this study is to determine the effect of policosanol on arterial blood pressure and its interaction with propranolol and nifedipine. METHODS: Single doses of policosanol (25, 50 and 200 mg/kg) orally administered to spontaneously hypertensive rats (SHR) did not significantly change arterial pressure. RESULTS: The study on pharmacological interactions between policosanol (200 mg/kg) and both antihypertensive agents revealed that pretreatment with high doses of policosanol significantly increased propranolol-induced hypotensive effects, while the effects of nifedipine remained unchanged. CONCLUSIONS: Our results show that policosanol does not antagonize the hypotensive effect of beta-blockers but it can increase the hypotensive effect of beta-blockers without modifying cardiac frequency.

Repeated REM sleep deprivation after chronic haloperidol administration in the rat.

Repeated haloperidol administration produces up-regulation of dopamine (DA) receptors. REM sleep deprivation (REMSD) does also, but in addition, has been shown to produce REM sleep rebound. Should DA receptor up-regulation play a role in REM sleep rebound, haloperidol could conceivably have effects similar to those observed following REMSD. This is the central question investigated in this study. Male Wistar rats were prepared for sleep recordings. They were randomly assigned to the following groups: group 1, REMSD by small platforms (40 h REMSD + 8 h recording); group 2, was the large platform control group (40 h in large platforms + 8 h of recording); group 3, received 2-week daily administration of haloperidol (3 mg/kg, i.p.) plus REMSD (40 h REMSD + 8 h of recording); group 4, 2-week administration of haloperidol (3 mg/kg) without sleep manipulation and at the end 40 h were allowed to elapse, following which 8 h of sleep recordings was carried out. In each group the sleep manipulation and/or sleep recordings were repeated five consecutive times. Repeated REMSD produced increases of REM sleep time after each recovery in group 1. Large platforms did not produce increases of REM sleep during the recovery trials. The 2-week administration of haloperidol plus REMSD prevented REM sleep rebound (group 3). The 2-week administration of haloperidol without sleep manipulation (group 4) produced a REM sleep reduction. Dopamine modulation seems not to be important for REM sleep rebound. Hypersensitivity of DA receptors developed after REMSD may be an epiphenomenon associated with this sleep manipulation, but seems not to participate in REM sleep enhancement after REMSD.