Cytokine profile of autologous platelet-derived eye drops in patients with ocular chronic graft-versus-host disease.

Ocular chronic GVHD is efficaciously treated with autologous platelet-derived eye drops. We investigated the cytokine content of eye drops produced using a non-gelified lysate obtained from autologous platelet-rich plasma in six patients with ocular GVHD. In both the responding (n = 4) and the resistant (n = 2) patients, the eye drops were significantly enriched with various growth factors, in amounts proportional with the platelet counts. In contrast, chemokine ligand and interleukin levels were similar to those of plasma. The non-responding patients showed the highest levels of chemokine (C-X-C motif) ligand (CXCL)10. These findings provide possible explanations for beneficial or detrimental effects of eye drops.

Pelvic and hind limb musculature of Staurikosaurus pricei (Dinosauria: Saurischia).

The study of pelvic and hind limb bones and muscles in basal dinosaurs is important for understanding the early evolution of bipedal locomotion in the group. The use of data from both extant and extinct taxa placed into a phylogenetic context allowed to make well-supported inferences concerning most of the hind limb musculature of the basal saurischian Staurikosaurus pricei Colbert, 1970 (Santa Maria Formation, Late Triassic of Rio Grande do Sul, Brazil). Two large concavities in the lateral surface of the ilium represent the origin of the muscles iliotrochantericus caudalis plus iliofemoralis externus (in the anterior concavity) and iliofibularis (in the posterior concavity). Muscle ambiens has only one head and originates from the pubic tubercle. The origin of puboischiofemoralis internus 1 possibly corresponds to a fossa in the ventral margin of the pré-acetabular iliac process. This could represent an intermediate stage prior to the origin of a true pré-acetabular fossa. Muscles caudofemorales longus et brevis were likely well developed, and Staurikosaurus is unique in bearing a posteriorly projected surface for the origin of caudofemoralis brevis.

Recovering missing data: estimating position and size of caudal vertebrae in Staurikosaurus pricei Colbert, 1970.

Missing data is a common problem in paleontology. It makes it difficult to reconstruct extinct taxa accurately and restrains the inclusion of some taxa on comparative and biomechanical studies. Particularly, estimating the position of vertebrae on incomplete series is often non-empirical and does not allow precise estimation of missing parts. In this work we present a method for calculating the position of preserved middle sequences of caudal vertebrae in the saurischian dinosaur Staurikosaurus pricei, based on the length and height of preserved anterior and posterior caudal vertebral centra. Regression equations were used to estimate these dimensions for middle vertebrae and, consequently, to assess the position of the preserved middle sequences. It also allowed estimating these dimensions for non-preserved vertebrae. Results indicate that the preserved caudal vertebrae of Staurikosaurus may correspond to positions 1-3, 5, 7, 14-19/15-20, 24-25/25-26, and 29-47, and that at least 25 vertebrae had transverse processes. Total length of the tail was estimated in 134 cm and total body length was 220-225 cm.

Effects of sympathectomy on myocardium remodeling and function.

OBJECTIVES: To evaluate the effects of sympathectomy on the myocardium in an experimental model. METHODS: The study evaluated three groups of male Wistar rats: control (CT; n=15), left unilateral sympathectomy (UNI; n=15), and bilateral sympathectomy (BIL; n=31). Sympathectomy was performed by injection of absolute alcohol into the space of the spinous process of the C7 vertebra. After 6 weeks, we assessed the chronotropic properties at rest and stress, cardiovascular autonomic modulation, myocardial and peripheral catecholamines, and beta-adrenergic receptors in the myocardium. The treadmill test consisted of an escalated protocol with a velocity increment until the maximal velocity tolerated by the animal was reached. RESULTS: The bilateral group had higher levels of peripheral catecholamines, and consequently, a higher heart rate (HR) and blood pressure levels. This suggests that the activation of a compensatory pathway in this group may have deleterious effects. The BIL group had basal tachycardia immediately before the exercise test and increased tachycardia at peak exercise (p<0.01); the blood pressure had the same pattern (p=0.0365). The variables related to autonomic modulation were not significantly different between groups, with the exception of the high frequency (HF) variable, which showed significant differences in CT vs UNI. There was no significant difference in beta receptor expression between groups. There was a higher concentration of peripheral norepinephrine in the BIL group (p=0.0001), and no significant difference in myocardial norepinephrine (p=0.09). CONCLUSION: These findings suggest that an extra cardiac compensatory pathway increases the sympathetic tonus and maintains a higher HR and higher levels of peripheral catecholamines in the procedure groups. The increase in HF activity can be interpreted as an attempt to increase the parasympathetic tonus to balance the greater sympathetic activity.

Point-of-care ultrasound for assessing arteriovenous fistula maturity in outpatient hemodialysis.

BACKGROUND: Point-of-care ultrasound in end-stage renal disease is on the rise. Presently the decision to cannulate an arteriovenous fistula is based on its duration since surgery and physical exam. This study examines the effects of point-of-care ultrasound on decreasing the time to arteriovenous fistula cannulation, time spent with a central venous catheter, and the complications and infections that arise. METHODS: Prospective point-of-care ultrasound patients were recruited between January 2015 and January 2018, while retrospective data (non-point-of-care ultrasound) were collected via chart review from patients who had fistula creation between November 2011 and May 2014. Patients had point-of-care ultrasound within 3 weeks after arteriovenous fistula creation and were followed for 1 year. Arteriovenous fistula cannulation was initiated when the following parameters were met: diameter > 6 mm (with no depreciable narrowing of more than 20% throughout), depth < 6 mm, and length > 6 cm. Demographic data, as well as time to cannulation and central venous catheter removal, number of infections, complications, and interventions were compared between point-of-care ultrasound and non-point-of-care ultrasound groups using unpaired t-test, chi-square, and Fisher exact test statistical analysis. RESULTS: A total of 37 patients with new arteriovenous fistulas were followed by point-of-care ultrasound compared to 29 non-point-of-care ultrasound patients. Point-of-care ultrasound patients had earlier cannulations (35.5 vs 63.3 days, p < 0.05), shorter central venous catheter duration (68.2 vs 98.3 days, p < 0.05), and less infections (12 vs 19) without differences in complication compared to the non-point-of-care ultrasound. CONCLUSION: Point-of-care ultrasound facilitates early and safe arteriovenous fistula cannulation leading to a reduction in central venous catheter time and risk of infection. Point-of-care ultrasound may also aid in earlier identification of complications and difficult cannulations.

BoLA-DRB3 genetic diversity in Highland Creole cattle from Bolivia.

The genetic diversity of the BoLA-DRB3 gene has been reported in different cattle breeds owing to its central role in the immune response. However, it is still unknown in hundreds of cattle breeds, especially native populations. Here, we studied BoLA-DRB3 genetic diversity in Highland Creole cattle (CrAl) from Western Bolivia, raised at altitudes between 3800 and 4200 m. DNAs from 48 CrAl cattle were genotyped for BoLA-DRB3 exon 2 alleles using polymerase chain reaction-sequence-based typing (PCR-SBT). The results were compared with 1341 previously reported data from Tropical Creole cattle and other breeds raised in the region. Twenty-three BoLA-DRB3 alleles were identified in CrAl, including the BoLA-DRB3*029:02 variant previously detected in other Creole cattle. Observed and expected heterozygosity were 0.87 and 0.93, respectively. Nucleotide diversity and the number of pairwise difference values were 0.078 and 19.46, respectively. The average number of nonsynonymous and synonymous substitutions were 0.037 and 0.097 for the entire BoLA-DRB3 exon 2, and 0.129 and 0.388 for the antigen-binding site, respectively. Venn analysis and the review of the IPD-MHC database and the literature showed that 2 of 64 alleles were only detected in CrAl, including BoLA-DRB3*029:01 previously reported in African cattle and *048:01 detected in Philippine cattle. Two additional alleles, BoLA-DRB3*007:02 and *029:02, were only present in CrAl and Lowland Creole cattle. Principal Component Analysis (PCA) showed that Bolivian Creole cattle breeds were closely located but they were distant from the Colombian Hartón del Valle Creole. FST analysis showed a low degree of genetic differentiation between Highland and Lowland Bolivian Creole cattle (FST = 0.015). The present results contribute to increasing our knowledge of BoLA-DRB3 genetic diversity in cattle breeds.

Effects of sympathectomy on myocardium remodeling and function

OBJECTIVES: To evaluate the effects of sympathectomy on the myocardium in an experimental model. METHODS: The study evaluated three groups of male Wistar rats: control (CT; n=15), left unilateral sympathectomy (UNI; n=15), and bilateral sympathectomy (BIL; n=31). Sympathectomy was performed by injection of absolute alcohol into the space of the spinous process of the C7 vertebra. After 6 weeks, we assessed the chronotropic properties at rest and stress, cardiovascular autonomic modulation, myocardial and peripheral catecholamines, and beta-adrenergic receptors in the myocardium. The treadmill test consisted of an escalated protocol with a velocity increment until the maximal velocity tolerated by the animal was reached. RESULTS: The bilateral group had higher levels of peripheral catecholamines, and consequently, a higher heart rate (HR) and blood pressure levels. This suggests that the activation of a compensatory pathway in this group may have deleterious effects. The BIL group had basal tachycardia immediately before the exercise test and increased tachycardia at peak exercise (p<0.01); the blood pressure had the same pattern (p=0.0365). The variables related to autonomic modulation were not significantly different between groups, with the exception of the high frequency (HF) variable, which showed significant differences in CT vs UNI. There was no significant difference in beta receptor expression between groups. There was a higher concentration of peripheral norepinephrine in the BIL group (p=0.0001), and no significant difference in myocardial norepinephrine (p=0.09). CONCLUSION: These findings suggest that an extra cardiac compensatory pathway increases the sympathetic tonus and maintains a higher HR and higher levels of peripheral catecholamines in the procedure groups. The increase in HF activity can be interpreted as an attempt to increase the parasympathetic tonus to balance the greater sympathetic activity.

Cabergoline in the treatment of early Parkinson's disease: results of the first year of treatment in a double-blind comparison of cabergoline and levodopa. The PKDS009 Collaborative Study Group.

Cabergoline is a potent D2 receptor agonist with a half-life of 65 hours that may provide continuous dopaminergic stimulation administered once daily. In this study, we randomized de novo Parkinson's disease (PD) patients to treatment with increasing doses of cabergoline (0.25 to 4 mg/d) or levodopa (100 to 600 mg/d) up to the optimal or maximum tolerated dose. Decreases of > 30% in motor disability (Unified Parkinson's Disease Rating Scale Factor III) versus baseline were considered indicative of clinical improvement. If 30% improvement was not achieved, levodopa/ carbidopa could be added on an open basis. Of the 208 patients entered in the cabergoline group, 175 remained in the study for 1 year at a mean dose of 2.8 mg/d; in the levodopa group, 176 of the 205 patients entered were still on study after 1 year at a mean dose of 468 mg/d. The proportion of patients requiring additional levodopa/carbidopa increased in the cabergoline group from 18% at 6 months to 38% at 1 year versus 10% (p = 0.05) at 6 months and 18% (p < 0.01) at 1 year in the levodopa group. The proportion of patients showing clinical improvement did not differ significantly between the two groups, or between the subgroups on monotherapy, at any endpoint. Irrespective of levodopa/carbidopa addition, 81% of patients in the cabergoline group and 87% of patients in the levodopa group were clinically improved at 1 year (p = 0.189); the corresponding figures for the subgroup on monotherapy were 79% in the cabergoline-treated patients and 86% in the levodopa-treated patients (p = 0.199). The mean difference versus baseline in Unified Parkinson's Disease Rating Scale Factor III scores in patients who remained on monotherapy up to 1 year was 12.6 (95% confidence interval [CI]: 10.8, 14.3) in the cabergoline group and 16.4 (95% CI: 14.8, 18.0) in the levodopa group. Adverse events occurred in 76% of patients on cabergoline and in 66% of patients on levodopa. The severity profile for reported events was similar for the two agents. The results of this study indicate that cabergoline treatment for up to 1 year is only marginally less effective than levodopa in the proportion of patients who can be treated in monotherapy. More than 60% of de novo PD patients could be managed on cabergoline alone up to 1 year. In the patients in whom levodopa/carbidopa was needed, the combination therapy provided efficacy similar to that obtained with levodopa alone, with a relevant sparing of levodopa.

Microbiology of acute arthropathies among children in Argentina: Mycoplasma pneumoniae and hominis and Ureaplasma urealyticum.

OBJECTIVE: To describe the isolation of mycoplasmas and ureaplasmas from synovial fluid in pediatric patients with joint disorders. METHODS: During 1 year 45 samples of synovial fluid, blood and urine were collected from 33 hospitalized pediatric patients up to 17 years old who had joint disorders. Mycoplasmas and ureaplasmas were isolated in joint fluid by culture methods. RESULTS: Of the 33 patients 12 (36%) had joint disorders associated with pathogens (bacteria, Mycoplasma/Ureaplasma, Chlamydia) present at the site of inflammation. Mycoplasma hominis and Ureaplasma urealyticum were isolated from 3 and 1% of joint fluid samples, respectively. M. pneumoniae was isolated from nasopharyngeal secretion in a patient with evidence of a reactive arthritis. CONCLUSION: Our results raise the question of the possible role of Mycoplasma as a cofactor in the triggering of inflammatory joint disease, as well as the hypothesis that arthropathies may be caused by chronic local infection. These findings may contribute to early diagnosis of the disease and initiation of specific treatment.

Irreparable rotator cuff tears: a novel classification system.

BACKGROUND: Irreparable rotator cuff tears can be managed by several approaches. However, current tear classifications fail to reflect the wide variety of their presentation, which has important clinical and prognostic implications. METHODS: We describe a novel classification system based on preoperative imaging findings and intraoperative observation where each cuff tendon (numbered sequentially: 1-supraspinatus, 2-infraspinatus, 3-teres minor, and 4-subscapularis) is assessed intraoperatively for reducibility to the footprint; tendons with reparable lesions are assessed for fatty degeneration (which predicts healing potential) and given a plus if degeneration is <50 % (Fuchs stage I-II/Goutallier stage 0-II) or a minus if it is ≥50 % (Fuchs stage III/Goutallier stage III-IV). RESULTS: The proposed system (1) allows more consistent and reproducible classification of cuff tears where at least one tendon is irreparable; (2) results in more accurate diagnosis; (3) guides in treatment selection; and (4) ensures better outcomes and realistic patient expectations. CONCLUSIONS: The novel classification system can contribute to develop increasingly exhaustive and reproducible classification models.

Arthroscopic Latarjet procedure: analysis of the learning curve.

BACKGROUND: The arthroscopic Latarjet procedure is an innovative technique that aims to combine the optimal results of the original open approach with those of arthroscopic stabilization. METHODS: We evaluated the learning curve and the preliminary results of the first 30 patients (29 males, 1 female; mean age 32 years, range 21-52) subjected to an arthroscopic Latarjet procedure at a mean follow-up of 13 months (range 6-22). RESULTS: Operative time fell significantly from 132 to 99 min (p < 0.001, t test) in the last 15 patients compared with the first 15 without significant differences in terms of Rowe score, patient satisfaction, complications, or graft placement. There were 21 (70 %) excellent and 9 (30 %) good outcomes according to the Rowe score. All complications (10 %) correlated with age >40 years (p = 0.002, Fisher's exact test). CONCLUSIONS: The arthroscopic Latarjet procedure is a standardized, hence reproducible technique whose complexity makes it suitable only for surgeons with solid experience in arthroscopy and shoulder surgery.

Electrocardiographic comparison of ventricular arrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy and right ventricular outflow tract tachycardia.

OBJECTIVES: The purpose of this study was to evaluate whether electrocardiographic characteristics of ventricular arrhythmias distinguish patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) from those with right ventricular outflow tract tachycardia (RVOT-VT). BACKGROUND: Ventricular arrhythmias in RVOT-VT and ARVD/C-VT patients can share a left bundle branch block/inferior axis morphology. METHODS: We compared the electrocardiographic morphology of ventricular tachycardia or premature ventricular contractions with left bundle branch block/inferior axis pattern in 16 ARVD/C patients with that in 42 RVOT-VT patients. RESULTS: ARVD/C patients had a significantly longer mean QRS duration in lead I (150 ± 31 ms vs. 123 ± 34 ms, p = 0.006), more often exhibited a precordial transition in lead V(6) (3 of 17 [18%] vs. 0 of 42 [0%] with RVOT-VT, p = 0.005), and more often had at least 1 lead with notching (11 of 17 [65%] vs. 9 of 42 [21%], p = 0.001). The most sensitive characteristics for the detection of ARVD/C were a QRS duration in lead I of ≥120 ms (88% sensitivity, 91% negative predictive value). QRS transition at V(6) was most specific at 100% (100% positive predictive value, 77% negative predictive value). The presence of notching on any QRS complex had 79% sensitivity and 65% specificity of (55% positive predictive value, 85% negative predictive value). In multivariate analysis, QRS duration in lead I of ≥120 ms (odds ratio [OR]: 20.4, p = 0.034), earliest onset QRS in lead V(1) (OR: 17.0, p = 0.022), QRS notching (OR: 7.7, p = 0.018), and a transition of V(5) or later (OR: 7.0, p = 0.030) each predicted the presence of ARVD/C. CONCLUSIONS: Several electrocardiographic criteria can help distinguish right ventricular outflow tract arrhythmias originating from ARVD/C compared with RVOT-VT patients.

Recovering missing data: estimating position and size of caudal vertebrae in Staurikosaurus pricei Colbert, 1970

Missing data is a common problem in paleontology. It makes it difficult to reconstruct extinct taxa accurately and restrains the inclusion of some taxa on comparative and biomechanical studies. Particularly, estimating the position of vertebrae on incomplete series is often non-empirical and does not allow precise estimation of missing parts. In this work we present a method for calculating the position of preserved middle sequences of caudal vertebrae in the saurischian dinosaur Staurikosaurus pricei, based on the length and height of preserved anterior and posterior caudal vertebral centra. Regression equations were used to estimate these dimensions for middle vertebrae and, consequently, to assess the position of the preserved middle sequences. It also allowed estimating these dimensions for non-preserved vertebrae. Results indicate that the preserved caudal vertebrae of Staurikosaurus may correspond to positions 1-3, 5, 7, 14-19/15-20, 24-25/25-26, and 29-47, and that at least 25 vertebrae had transverse processes. Total length of the tail was estimated in 134 cm and total body length was 220-225 cm.

Dados lacunares são um problema comum na paleontologia. Eles dificultam a reconstrução acurada de táxons extintos e limitam a inclusão de alguns táxons em estudos comparativose biomecânicos. Particularmente, estimar a posição de vértebras em séries incompletas tem sido feito com base em métodos não empíricos que não permitem estimar corretamente as partes ausentes. Neste trabalho apresentamos uma metodologia que permite estimar a posição de sequências médias preservadas de vértebras caudais no dinossauro saurísquio Staurikosaurus pricei, com base no comprimento e altura dos centros das vértebras anteriores e posteriores preservadas. Equações de regressão foram usadas para estimar essas dimensões para as vértebras médias e, consequentemente, para posicionar as sequências médias preservadas e para estimar o tamanho das vértebras não preservadas. Os resultados indicam que as vértebras caudais preservadas de Staurikosaurus corresponderiam às posições 1-3, 5, 7, 14-19/15-20, 24-25/25-26 e 29-47, e que pelo menos 25 vértebras possuíam processos transversos. O comprimento total da cauda foi estimado em 134 cm e o comprimento total do corpo em 220-225 cm.

Pelvic and hind limb musculature of Staurikosaurus pricei (Dinosauria: Saurischia)

The study of pelvic and hind limb bones and muscles in basal dinosaurs is important for understanding the early evolution of bipedal locomotion in the group. The use of data from both extant and extinct taxa placed into a phylogenetic context allowed to make well-supported inferences concerning most of the hind limb musculature of the basal saurischian Staurikosaurus pricei Colbert, 1970 (Santa Maria Formation, Late Triassic of Rio Grande do Sul, Brazil). Two large concavities in the lateral surface of the ilium represent the origin of the muscles iliotrochantericus caudalis plus iliofemoralis externus (in the anterior concavity) and iliofibularis (in the posterior concavity). Muscle ambiens has only one head and originates from the pubic tubercle. The origin of puboischiofemoralis internus 1 possibly corresponds to a fossa in the ventral margin of the pré-acetabular iliac process. This could represent an intermediate stage prior to the origin of a true pré-acetabular fossa. Muscles caudofemorales longus et brevis were likely well developed, and Staurikosaurus is unique in bearing a posteriorly projected surface for the origin of caudofemoralis brevis.

O estudo da musculatura pelvica e do membro posterior em dinossauros basais e importante para entender a evolução inicial do bipedalismo em dinossauros Saurischia. Empregando uma metodologia que tem como base dados obtidos a partir de taxons viventes e extintos posicionados em um contexto filogenetico, foi possivel fazer inferencias bem suportadas relativas a maior parte dos musculos do membro posterior do dinossauro Saurischia basal Staurikosaurus pricei Colbert, 1970 (Formação Santa Maria, Triassico Superior do Rio Grande do Sul, Brasil). Duas grandes concavidades na superficie lateral do ilio correspondem a origem dos musculos iliotrochantericus caudalis e iliofeoralis externus (compartilhando a concavidade anterior) e para o musculo iliofibularis (na concavidade posterior). O musculo ambiens apresenta apenas um ramo que se origina no tuberculo pubico. A origem provavel do musculo puboischiofemoralis internus 1 esta localizada numa fossa na margem ventral do processo pré-acetabular do ilio, representando um estagio anterior a formacão da verdadeira fossa pré-acetabular. Os musculos caudofemorales longus et brevis sao bem desenvolvidos e Staurikosaurus e unico por apresentar a superficie de origem do musculo caudofeoralis brevis projetada e expandida posteriormente.

Bronchodilator activity in vivo and in vitro of four 13,14-didehydro-PGE2 analogues.

The bronchodilator activity of four analogues of PGE2: 13,14-didehydro-PGE2 (I), 20-methyl-13,14-didehydro-PGE2 (II), 16 S-methyl-13,14-didehydro-PGE2 (III) and 16 R-methyl-13,14-didehydro-PGE2 (IV) was studied in vivo and in vitro. The potency of III and IV when administered by aerosol to conscious guinea pigs was four times that of PGE2 in protecting against histamine-induced convulsion; I and II were less active. Compound III administered by aerosol to anaesthetized guinea pigs was six times more potent than PGE2 in protecting against i.v. histamine-induced increase of intractracheal pressure and the effect was longer-lasting. All the compounds caused relaxation of carbachol-induced tone in isolated guinea pig tracheal strips.