Hospital Clínico de la Universidad Católica

OBJECTIVE: Changes in the maternal plasma concentrations of angiogenic (placental growth factor (PlGF) and vascular endothelial growth factor (VEGF)) and anti-angiogenic factors (sEng and vascular endothelial growth factor receptor-1 (sVEGFR-1)) precede the clinical presentation of preeclampsia. This study was conducted to examine the role of maternal plasma PlGF, sEng, and sVEGFR-1 concentrations in early pregnancy and midtrimester in the identification of patients destined to develop preeclampsia. METHODS: This longitudinal cohort study included 1622 consecutive singleton pregnant women. Plasma samples were obtained in early pregnancy (6-15 weeks) and midtrimester (20-25 weeks). Maternal plasma PlGF, sEng, and sVEGFR-1 concentrations were determined using sensitive and specific immunoassays. The primary outcome was the development of preeclampsia. Secondary outcomes included term, preterm, and early-onset preeclampsia. Receiving operating characteristic curves, sensitivity, specificity, positive and negative likelihood ratios, and multivariable logistic regression were applied. A p-value of <0.05 was considered significant. RESULTS: (1) The prevalence of preeclampsia, term, preterm, (<37 weeks) and early-onset preeclampsia (<34 weeks) was 3.8 (62/1622), 2.5 (40/1622), 1.4 (22/1622) and 0.6% (9/1622), respectively; (2) Higher likelihood ratios were provided by ratios of midtrimester plasma concentrations of PlGF, sEng, and sVEGFR-1 than single analytes; (3) Individual angiogenic and anti-angiogenic factors did not perform well in the identification of preeclampsia as a whole; in particular, they perform poorly in the prediction of term preeclampsia; (4) In contrast, a combination of these analytes such as the PlGF/sEng ratio, its delta and slope had the best predictive performance with a sensitivity of 100%, a specificity of 98-99%, and likelihood ratios for a positive test of 57.6, 55.6 and 89.6, respectively, for predicting early-onset preeclampsia. CONCLUSIONS: (1) The PlGF/sEng ratio and its delta and slope had an excellent predictive performance for the prediction of early-onset preeclampsia, with very high likelihood ratios for a positive test result and very low likelihood ratios for a negative test result; and (2) Although the positive likelihood ratios are high and the positive predictive values low, the number of patients needed to be closely followed is 4:1 for the PlGF/sEng ratio and 3:1 for the slope of PlGF/sEng.

Directed cell migration is crucial for development, but most of our current knowledge is derived from in vitro studies. We analyzed how neural crest (NC) cells migrate in the direction of their target during embryonic development. We show that the proteoglycan Syndecan-4 (Syn4) is expressed in the migrating neural crest of Xenopus and zebrafish embryos. Loss-of-function studies using an antisense morpholino against syn4 show that this molecule is required for NC migration, but not for NC induction. Inhibition of Syn4 does not affect the velocity of cell migration, but significantly reduces the directional migration of NC cells. Furthermore, we show that Syn4 and PCP signaling control the directional migration of NC cells by regulating the direction in which the cell protrusions are generated during migration. Finally, we perform FRET analysis of Cdc42, Rac and RhoA in vitro and in vivo after interfering with Syn4 and PCP signaling. This is the first time that FRET analysis of small GTPases has been performed in vivo. Our results show that Syn4 inhibits Rac activity, whereas PCP signaling promotes RhoA activity. In addition, we show that RhoA inhibits Rac in NC cells. We present a model in which Syn4 and PCP control directional NC migration by, at least in part, regulating membrane protrusions through the regulation of small GTPase activities.

PURPOSE: To determine the concentration of interleukins (IL-1beta and -6) and matrix metalloproteinase 9 (pro-MMP-9) in the tears of patients with different ocular surface diseases and to examine the possible relationship between the disorders and molecular inflammation. METHODS: 77 patients diagnosed as having different ocular surface disorders and 18 normal control subjects were studied. Patients were routinely examined and separated into 5 groups: (1) control, (2) blepharitis, (3) ocular allergic disease, (4) dry eye and (5) conjunctivochalasis. Ten microliters of tears were collected by a Weck cell sponge. The concentrations of IL-1beta, IL-6 and pro-MMP-9 were measured by enzyme-linked immunosorbent assay, and the MMP-9 activity was evaluated with gelatin zymography. RESULTS: Levels of IL-1beta and IL-6 in tear fluid were significantly higher in conjunctivochalasis (p = 0.0062 and p = 0.0134) than in the control group. Pro-MMP-9 levels were significantly elevated in blepharitis (p = 0.013), in allergic eye disease, in dry eye and in conjunctivochalasis (all p < 0.001), in comparison to controls. CONCLUSIONS: Pro-MMP-9 levels in tears are elevated in all of the studied pathologies especially in ocular allergy and conjunctivochalasis. However, IL-1beta and IL-6 were only found to be overexpressed in conjunctivochalasis. These findings illustrate the selective implication of different molecules in each disorder.

It has been demonstrated that during pregnancy expiratory reserve volume (ERV) decreases and minute ventilation (VE) increases initially and then stabilizes. In order to determine the role of thoracoabdominal mechanics, control of breathing, and inspiratory muscle function in these alterations, we studied inspiratory pressures, lung volumes, thoracic configuration, and respiratory drive in 18 normal pregnant women at Weeks 13, 21, 30, and 37 of pregnancy. Ten of them were studied 6 months after delivery. Transdiaphragmatic pressure (Pdi) was measured at Week 37 and 3 months after delivery in an additional group of seven women. VE as well as VT/TI increased early during gestation and remained unchanged thereafter. In contrast, mouth occlusion pressure (P0.1) increased progressively during pregnancy, from 1.53 +/- 0.16 (mean +/- SE) to 2.02 +/- 0.18 cm H2O, and fell significantly to 1.1 +/- 0.15 cm H2O after delivery, indicating that effective respiratory impedance increases during pregnancy. Mean P0.1 correlated with progesterone plasma levels (r = 0.918 p less than 0.05). No changes in Plmax, PEmax, and Pdimax, were observed. End-expiratory gastric pressure (Pga) increases significantly during pregnancy: 11.8 +/- 0.8 versus 8.4 +/- 1.12 cm H2O after delivery (p less than 0.012). This increment was correlated with the fall in ERV observed in late pregnancy (r = 0.74 p less than 0.05). Our results demonstrate that during pregnancy ventilatory drive and respiratory impedance increase with the consequent stabilization of VE, but our data do not permit us to differentiate whether the increment in P0.1 is secondary to the increase in impedance or to the rise in progesterone. Respiratory muscle function remains normal despite the alteration of thoracic configuration.

Several recent reports have indicated an increased prevalence of gallstones in association with pregnancy. If these reports are true, the early puerperium should be a favorable time to detect the disease in its initial stages and follow its natural course. Accordingly, the gallbladder was examined by ultrasound in 980 women during the immediate postpartum period and in 150 nulliparous, age-matched healthy volunteers. Gallstones were detected in 12.2% of the puerperal women and in 1.3% of the control group. In 70 patients who had stones in a functioning gallbladder, 22 (31%) had had attacks of biliary colic. The history of pain was more common in patients with stones greater than 10 mm in diameter. Forty-one women with small stones (< 10 mm) were followed clinically and ultrasonographically for between 6 and 24 (mean = 8.7) mo. All remained pain-free, and in twelve subjects (29%) the stones disappeared. Gallbladder bile was examined in 11 normal volunteers (controls) immediately after delivery and in 19 women with small stones 39 +/- 6 days postpartum. Bile was saturated with cholesterol in the controls and was unsaturated in patients with gallstones. We conclude that in our population pregnancy is a very important pathogenetic factor favoring gallstone formation. Attacks of biliary colic appear early and frequently in young Chilean women with this disease. Unexplained disappearance of small stones frequently occurs: in some cases it is likely to be the result of spontaneous dissolution because bile becomes unsaturated within a few weeks of delivery.

A velocity k-space formalism facilitates the analysis of flow effects for imaging sequences involving time-varying gradients such as echo-planar and spiral. For each sequence, the velocity k-space trajectory can be represented by kv(kr); that is, its velocity-frequency (kv) position as a function of spatial-frequency (kr) position. In an echo-planar sequence, kv is discontinuous and asymmetric. However, in a spiral sequence, kv is smoothly varying, circularly symmetric, and small near the kr origin. To compare the effects of these trajectory differences, simulated images were generated by computing the k-space values for an in-plane vessel with parabolic flow. Whereas the resulting echo-planar images demonstrate distortions and ghosting that depend on the vessel orientation, the spiral images exhibit minimal artifacts.

We present a detailed analysis from new multi-wavelength observations of the exceptional galaxy cluster ACT-CL J0102-4915, likely the most massive, hottest, most X-ray luminous and brightest Sunyaev-Zel'dovich (SZ) effect cluster known at redshifts greater than 0.6. The Atacama Cosmology Telescope (ACT) collaboration discovered ACT-CL J0102-4915 as the most significant Sunyaev-Zeldovich (SZ) decrement in a sky survey area of 755 square degrees. Our VLT/FORS2 spectra of 89 member galaxies yield a cluster redshift, z = 0.870, and velocity dispersion, sigma(gal) +/- 1321 106 km s-1. Our Chandra observations reveal a hot and X-ray luminous system with an integrated temperature of T(X) = 14:5 +/- 0:1 keV and 0.5 2.0 keV band luminosity of L(X) = (2:19 0:11) 1045 h(exp -2)70erg s-1. We obtain several statistically consistent cluster mass estimates; using empirical mass scaling relations with velocity dispersion, X-ray Y(X) , and integrated SZ distortion, we estimate a cluster mass of M(200) = (2:16 +/- 0:32) 10(exp 15) h(exp-1) 70M compared to the Sun. We constrain the stellar content of the cluster to be less than 1% of the total mass, using Spitzer IRAC and optical imaging. The Chandra and VLT/FORS2 optical data also reveal that ACT-CL J0102-4915 is undergoing a major merger between components with a mass ratio of approximately 2 to 1. The X-ray data show significant temperature variations from a low of 6:6 +/- 0:7 keV at the merging low-entropy, high-metallicity, cool core to a high of 22 +/- 6 keV. We also see a wake in the X-ray surface brightness and deprojected gas density caused by the passage of one cluster through the other from which we estimate a merger speed of around 1300 km s(exp -1) for an assumed merger timescale of 1 Gyr. ACTCL J0102-4915 is possibly a high-redshift analog of the famous Bullet Cluster. Such a massive cluster at this redshift is rare, although consistent with the standard CDM cosmology in the lower part of its allowed mass range. Massive, high-redshift mergers like ACT-CL J0102-4915 are unlikely to be reproduced in the current generation of numerical N-body cosmological simulations.

Saccharomyces cerevisiae is widely used as a probiotic compound. Clinical data suggest that this agent is safe and effective. We report two cases of fungemia caused by S. cerevisiae occurring in immunosuppressed patients treated orally with S. boulardii Molecular typing confirmed clonality in isolate strains from patients and the capsule. Physicians caring for immunosuppressed patients must be aware of this potential serious complication of probiotic use.

BACKGROUND: Using multinational collections of methicillin-susceptible Staphylococcus aureus (MSSA) isolates from infective endocarditis (IE) and soft tissue infections (STIs), we sought to (1) validate the finding that S. aureus in clonal complex (CC) 30 is associated with hematogenous complications and (2) test the hypothesis that specific genetic characteristics in S. aureus are associated with infection severity. METHODS: IE and STI isolates from 2 cohorts were frequency matched by geographic origin. Isolates underwent spa typing to infer CC and multiplex polymerase chain reaction for presence of virulence genes. RESULTS: 114 isolate pairs were genotyped. IE isolates were more likely to be CC30 (19.5% vs 6.2%; P = .005) and to contain 3 adhesins (clfB, cna, map/eap; P < .0001 for all) and 5 enterotoxins (tst, sea, sed, see, and sei; P ≤ .005 for all). CC30 isolates were more likely to contain cna, tst, sea, see, seg, and chp (P < .05 for all). CONCLUSIONS: MSSA IE isolates were significantly more likely to be CC30 and to possess a distinct repertoire of virulence genes than MSSA STI isolates from the same region. The genetic basis of this association requires further study.

OBJECTIVE: To determine the prevalence and clinical significance of amniotic fluid (AF) 'sludge' observed during transvaginal ultrasound examination of the cervix in patients with preterm labor and intact membranes, and in those with uncomplicated pregnancies. METHODS: This retrospective study included patients with preterm labor and intact membranes (n = 84) and those with uncomplicated term pregnancies (n = 298). The outcome variables included the occurrence of documented microbial invasion of the amniotic cavity (MIAC), histological chorioamnionitis, examination-to-delivery interval, admission to the neonatal intensive care unit (NICU), a composite neonatal morbidity, perinatal death, and delivery within 48 h, 7 days, and < 35 weeks and < 32 weeks. Statistical analysis included Chi-square test, stepwise logistic regression analysis and survival analysis. RESULTS: The prevalence of AF 'sludge' was 1% (3/298) in patients with uncomplicated term pregnancies and 22.6% (19/84) in those with preterm labor and intact membranes. Among patients with preterm labor and intact membranes: (1) cervical length < or = 15 mm was present in 58.3% (49/84) of the patients; (2) the prevalence of MIAC and histological chorioamnionitis was 12.1% (7/58) and 32.9% (25/76), respectively; (3) the rate of spontaneous preterm delivery within 48 h, 7 days, and < 32 weeks and < 35 weeks of gestation was 13.6% (8/59), 28.8% (17/59), 39.5% (17/43) and 50.8% (30/59), respectively; (4) patients with AF 'sludge' had a higher frequency of positive AF cultures [33.3% (6/18) vs. 2.5% (1/40), P = 0.003] and histological chorioamnionitis [77.8% (14/18) vs. 19% (11/58), P < 0.001] than those without AF 'sludge'; (5) a higher proportion of neonates born to patients with AF 'sludge' was admitted to the NICU [64.3% (9/14) vs. 12.9% (8/62), P < 0.01], had a composite neonatal morbidity [36.8% (7/19) vs. 13.8% (9/65), P = 0.04] and died in the perinatal period [36.8% (7/19) vs. 4.6% (3/65), P = 0.001] than those born to women without 'sludge'; (6) a higher proportion of patients with AF 'sludge' had spontaneous delivery within 48 h [42.9% (6/14) vs. 4.4% (2/45), P = 0.001], within 7 days [71.4% (10/14) vs. 15.6% (7/45), P < 0.001], < 32 weeks [75% (9/12) vs. 25.8% (8/31), P = 0.005] and < 35 weeks [92.9% (13/14) vs. 37.8% (17/45), P < 0.001] than those without AF 'sludge'; and (7) patients with AF 'sludge' had a shorter examination-to-delivery interval than those without AF 'sludge' [AF 'sludge' median, 1 (IQR, 1-5) days vs. no AF 'sludge' median, 33 (IQR, 18-58) days; P < 0.001]. CONCLUSION: The presence of AF 'sludge' in patients with preterm labor and intact membranes is a risk factor for MIAC, histological chorioamnionitis and impending preterm delivery.

Two previous uncontrolled studies have suggested that noninvasive mechanical ventilation (NIMV) in patients with hypercapnic chronic obstructive pulmonary disease (COPD) improves arterial blood gas tensions by decreasing lung hyperinflation with the consequent reduction in inspiratory loads and changes in ventilatory pattern. The aim of this randomised placebo-controlled study was to determine whether these mechanisms play a pivotal role in the effects of NIMV on arterial blood gases. Thirty-six stable hypercapnic COPD patients were randomly allocated to NIMV or sham NIMV. A 2-week run-in period was followed by a 3-week study period, during which ventilation was applied 3 h x day(-1), 5 days a week. Arterial blood gases, spirometry, lung volumes, and respiratory mechanics were measured before and after application of NIMV. Patients submitted to NIMV showed changes (mean (95% confidence interval)) in daytime arterial carbon dioxide tension (Pa,CO2) and arterial oxygen tension of -1.12 (-1.52-0.73) kPa (-8.4 (-11.4-5.5) mmHg) and 1.14 (0.70-1.50) kPa (8.6 (5.3-11.9) mmHg), respectively. Total lung capacity, functional residual capacity (FRC) and residual volume were found to be reduced by 10 (7-13), 25 (18-31), and 36 (27-45)% of their predicted value, respectively, whereas forced expiratory volume in one second and forced vital capacity increased by 4 (1.5-6.9) and 9 (5-13)% pred, respectively. Tidal volume (VT) increased by 181 (110-252) mL. All of the above changes were significant compared with sham NIMV. Changes in Pa,CO2 were significantly related to changes in dynamic intrinsic positive end-expiratory pressure, inspiratory lung impedance, VT and FRC. It was concluded that the beneficial effects of noninvasive mechanical ventilation could be explained by a reduction in lung hyperinflation and inspiratory loads.

The usefulness of inspiratory muscle training (IMT) in chronic airflow limitation (CAL) patients is a controversial issue, mainly due to differences in the training load. To further evaluate this aspect, we studied the effect of the magnitude of the load using a threshold pressure trainer. Ten CAL patients (5 males, 5 females) 67 +/- 2 yrs (mean +/- SEM) and forced expiratory volume in one second (FEV1) 36 +/- 2% pred, were trained for 30 min a day using a load of 30% of their maximal inspiratory mouth pressure (PImax) (Group 1). Another 10 CAL patients (5 males, 5 females), 73 +/- 2 yrs and FEV1 37 +/- 2% pred), were trained using only 12% of their PImax (Group 2). Training was assessed by PImax, inspiratory muscle power output (IMPO), sustainable inspiratory pressure (SIP), maximal inspiratory flow rate (VImax), pattern of breathing during loaded breathing, Mahler's dyspnoea score, and the 6 min walking distance (6MWD). After 5 weeks of training, Group 1 exhibited significant increments in: PImax (34 +/- 11%); IMPO (92 +/- 16%); SIP (36 +/- 9%); and VImax (34 +/- 13%). Dyspnoea was also reduced, and the 6MWD increased by 48 +/- 22 m. We observed no significant changes in Group 2. During loaded breathing, Group 1 showed a significant increment in tidal volume (VT) and mean inspiratory flow (VT/TI), and a reduction in inspiratory time (TI). In Group 2, VT and VT/TI also increased significantly, but the breathing frequency increased with a reduction of expiratory time.(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND: We have observed an increase in hepatotoxicity (DILI) reporting related to the use of anabolic androgenic steroids (AAS) for bodybuilding. AIM: To characterise phenotype presentation, outcome and severity of AAS DILI. METHODS: Data on 25 cases of AAS DILI reported to the Spanish (20) and Latin-American (5) DILI Registries were collated and compared with previously published cases. RESULTS: AAS DILI increased from representing less than 1% of the total cases in the Spanish DILI Registry in the period 2001-2009 to 8% in 2010-2013. Young men (mean age 32 years), requiring hospitalisation, hepatocellular injury and jaundice were predominating features among the AAS cases. AAS DILI caused significantly higher bilirubin values independent of type of damage when compared to other drug classes (P = 0.001). Furthermore, the cholestatic AAS cases presented significantly higher mean peak bilirubin (P = 0.029) and serum creatinine values (P = 0.0002), compared to the hepatocellular cases. In a logistic regression model, the interaction between peak bilirubin values and cholestatic damage was associated with the development of AAS-induced acute kidney impairment (AKI) [OR 1.26 (95% CI: 1.035-1.526); P = 0.021], with 21.5 ×ULN being the best bilirubin cut-off point for predicting AKI risk (AUCROC 0.92). No fatalities occurred. CONCLUSIONS: Illicit recreational AAS use is a growing cause of reported DILI that can lead to severe hepatic and renal injury. AAS DILI is associated with a distinct phenotype, characterised by considerable bilirubin elevations independent of type of damage. Although hepatocellular injury predominates, acute kidney injury develops in cholestatic cases with pronounced jaundice.

A B S T R A C T It is generally assumed that hepatic transport of bile acids is a carrier-mediated process. However, the basic mechanisms by which these organic anions are translocated across the liver cell surface mem- brane are not well understood. Since carrier-mediated transport involves binding of the transported molecule to specific receptor sites, we have investigated the possibility that bile acid receptors are present in liver sur- face membranes.

BACKGROUND: Protease inhibitor treatment of human immunodeficiency virus (HIV)-infected individuals has been linked to the development of lipodystrophy. The effects of atazanavir on body fat distribution and related metabolic parameters were examined in antiretroviral-naive patients. METHODS: HIV-positive patients with CD4 cell counts > or = 100 cells/mm3 were randomized to 1 of 2 treatment arms: (1) atazanavir, 400 mg given once daily, plus efavirenz placebo; or (2) efavirenz, 600 mg given once daily, plus atazanavir placebo; each drug was administered with fixed-dose zidovudine (300 mg) and lamivudine (150 mg) given twice daily, and patients were treated for at least 48 weeks. Fat distribution measurements (visceral adipose tissue [VAT], subcutaneous adipose tissue [SAT], and total adipose tissue [TAT], as measured by computed tomography; and appendicular fat, truncal fat, and total fat levels, as measured by dual-energy x-ray absorptiometry), metabolic measurements (cholesterol and fasting triglyceride levels), and measurements of insulin resistance (fasting glucose and fasting insulin levels) were made at baseline and at week 48 of treatment for a subgroup of 111 atazanavir recipients and 100 efavirenz recipients. RESULTS: Atazanavir and efavirenz treatments resulted in minimal to modest increases in fat accumulation, as measured by VAT, SAT, TAT, appendicular fat, truncal fat, and total fat levels; results were comparable in both arms. In addition, atazanavir was associated with none of the metabolic abnormalities seen with many other protease inhibitors. CONCLUSIONS: Use of atazanavir for 48 weeks neither resulted in abnormal fat redistribution in antiretroviral-naive patients nor induced other metabolic disturbances commonly associated with HIV-related lipodystrophy. Longer-term assessments (e.g., at 96 weeks) will be important to confirm these findings.

<i>Context. <i/>The standard prescription of angular momentum loss in compact binaries assumes magnetic braking to be very efficient as long as the secondary star has a radiative core, but to be negligible if the secondary star is fully convective. This prescription has been developed to explain the orbital period gap observed in the orbital period distribution of cataclysmic variables but has so far not been independently tested. Because the evolutionary time-scale of post common envelope binaries (PCEBs) crucially depends on the rate of angular momentum loss, a fundamental prediction of the disrupted magnetic braking theory is that the relative number of PCEBs should dramatically decrease for companion-star masses exceeding the mass that corresponds to the fully-convective boundary. <i>Aims. <i/>We present the results of a large survey of PCEBs among white dwarf/main sequence (WDMS) binaries that allows us to determine the fraction of PCEBs as a function of secondary star mass and therewith to ultimately test the disrupted magnetic braking hypothesis. <i>Methods. <i/>We obtained multiple spectroscopic observations spread over at least two nights for 670 WDMS binaries. Systems showing at least 3<i>σ<i/> radial velocity variations are considered to be strong PCEB candidates. Taking into account observational selection effects we compare our results with the predictions of binary population simulations.<i>Results. <i/>Among the 670 WDMS binaries we find 205 strong PCEB candidates. The fraction of PCEBs among WDMS binaries peaks around <i>M<i/><sub>sec<sub/> ~ 0.25 and steeply drops towards higher mass secondary stars in the range of <i>M<i/><sub>sec<sub/> = 0.25–0.4 . <i>Conclusions. <i/>The decrease of the number of PCEBs at the fully convective boundary strongly suggests that the evolutionary time scales of PCEBs containing fully convective secondaries are significantly longer than those of PCEBs with secondaries containing a radiative core. This is consistent with significantly reduced magnetic wind braking of fully convective stars as predicted by the disrupted magnetic braking scenario.

VLT spectra of 14 luminous compact galaxies (LCGs) reveal strong metallic absorption line sytems as well as narrow and intense emission lines. Their gas extinction is found to be large (AV ∼ 1.5 mag) leading to an upward revision of their star formation rate (SFR) to an average value of ∼ 40 M⊙yr−1. Large extinction values are also supported by the large rate of detection in one field observed by ISO. Gas metal abundances in LCGs have about half the solar value. LCG absorption spectra can be synthesized with a mix of a few Gyr old and relatively metal-rich (generally solar to over-solar values) stellar population and a younger stellar population (&amp;lt; 5×108 years) having a metal abundance similar to that of the gas. We argue that LCGs are the progenitors of present-day spiral bulges. LCGs have masses and light concentrations similar to those of present-day bulges. They could have been formed entirely during a period of a few Gyr prior to the epoch of their observations if the star formation has been sustained at the observed rate. As in present-day galactic bulges, LCG stars show a wide range of abundances. Thus, observing LCGs allows us to directly witness an important stage in the formation of a massive galaxy, the building of the bulge prior to that of the disk.

The safety, effectiveness and duration of a percutaneous ilioinguinal-iliohypogastric nerve block with 10 ml 0.5% bupivacaine, as a method for postoperative analgesia, were studied prospectively in adult patients undergoing unilateral inguinal herniorrhaphy under spinal anesthesia. Group I (n = 20) blocked patients were compared with Group II (n = 25), non-blocked control patients. A blinded observer assessed pain scores and analgesic requirements after surgery. Group I patients had less pain at 3, 6, 24 and 48 hours after surgery and also required less analgesics during the first two postoperative days. This technique appears to be a simple and safe method for providing effective and long-lasting postoperative analgesia following inguinal hernia repair in adults.

Abstract We examine the incentives of atomistic producers to differentiate and collectively market products. We analyze market and welfare effects of alternative producer organizations, discuss circumstances under which they will evolve, and describe implications for the ongoing debate between the EU and the United States. As fixed costs of development and marketing increase and the anticipated market size falls, it becomes essential to increase the producer organization's ability to control supply to cover the fixed costs associated with the introduction of differentiated products. Counterintuitively, stronger property right protection for producer organizations may enhance welfare even after a differentiated product has been developed.

BACKGROUND: Although clinicians sometimes choose amiodarone to convert atrial fibrillation (AF) to sinus rhythm, no current and comprehensive systematic review has summarized its effectiveness. OBJECTIVE: To review the effectiveness of amiodarone in converting AF to sinus rhythm over a 4-week period. METHODS: Two reviewers conducted a systematic search for randomized trials in databases, complemented by hand searches and contact with experts. Selected trials compared amiodarone with placebo, digoxin, or calcium channel blockers for conversion of AF to sinus rhythm. Reviewers evaluated the methodology and extracted data from each primary study. RESULTS: Twenty-one studies met eligibility criteria. Duration of AF proved to be a source of heterogeneity, leading to 2 analyses. The relative risk (RR) for achieving sinus rhythm was 4.33 (95% confidence interval [CI], 2.76-6.77) for trials with mean AF duration of greater than 48 hours and 1.40 (95% CI, 1.25-1.57) for those with AF of 48 hours or less. The risk differences for these 2 groups were 27% and 26%, respectively, yielding a number needed to treat of 4 for both groups. The low control event rate among trials with long duration of AF, compared with that of trials with a duration of 48 hours or less, explained the difference in the RR for conversion. We found that the size of the left atrium, presence of cardiovascular disease, and protocols of amiodarone administration did not influence the magnitude of effect. Serious adverse events were infrequent. CONCLUSIONS: Amiodarone is effective for converting AF to sinus rhythm in a wide range of patients. Although use of amiodarone is apparently safe, safety data are too scarce for definitive conclusions.