A randomised controlled trial of periconal eye blockade with or without ultrasound guidance.

We randomly allocated 129 participants with normal eyes to periconal blockade with (n = 69) or without (n = 60) ultrasound guidance before cataract surgery. There was no difference in the rates of complication, 1/69 and 0/60, respectively, p = 1.0. The rate of intraconal needle placement was 1/69 with ultrasound and 12/60 without ultrasound, a relative risk (95% CI) of 0.07 (0.01-0.55), p < 0.0001.

Dydrogesterone does not reverse the cardiovascular benefits of percutaneous estradiol.

OBJECTIVE: To evaluate the influence of dydrogesterone on estimated cardiovascular risk of users of hormone replacement therapy (HRT) (with percutaneous 17ß-estradiol in monotherapy and in combination with dydrogesterone) and HRT non-users through the Framingham score tool for a period of 2 years. METHODS: Framingham scores were calculated from the medical records of patients treated for at least 2 years with 17ß-estradiol alone or in combination with dydrogesterone, along with HRT non-users, through the analysis of patient medical records, followed for at least 2 years at Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione. RESULTS: Improvements in lipid profile, glucose and blood pressure levels, which reduced the estimated cardiovascular risk, were observed in the 17ß-estradiol group. Similar changes were observed in the users of 17ß-estradiol + dydrogesterone, suggesting that this progestogen does not attenuate the effects caused by 17ß-estradiol. CONCLUSIONS: Both HRT groups showed a reduction in their Framingham score. In contrast to data from other HRT investigations on cardiovascular risk, these formulations proved to be safe, even in the first year of use.

Treatment of advanced hepatocellular carcinoma with very low levels of amplitude-modulated electromagnetic fields.

BACKGROUND: Therapeutic options for patients with advanced hepatocellular carcinoma (HCC) are limited. There is emerging evidence that the growth of cancer cells may be altered by very low levels of electromagnetic fields modulated at specific frequencies. METHODS: A single-group, open-label, phase I/II study was performed to assess the safety and effectiveness of the intrabuccal administration of very low levels of electromagnetic fields amplitude modulated at HCC-specific frequencies in 41 patients with advanced HCC and limited therapeutic options. Three-daily 60-min outpatient treatments were administered until disease progression or death. Imaging studies were performed every 8 weeks. The primary efficacy end point was progression-free survival 6 months. Secondary efficacy end points were progression-free survival and overall survival. RESULTS: Treatment was well tolerated and there were no NCI grade 2, 3 or 4 toxicities. In all, 14 patients (34.1%) had stable disease for more than 6 months. Median progression-free survival was 4.4 months (95% CI 2.1-5.3) and median overall survival was 6.7 months (95% CI 3.0-10.2). There were three partial and one near complete responses. CONCLUSION: Treatment with intrabuccally administered amplitude-modulated electromagnetic fields is safe, well tolerated, and shows evidence of antitumour effects in patients with advanced HCC.

Time of Dropout From the Liver Transplant List in Patients With Hepatocellular Carcinoma: Clinical Behavior According to Tumor Characteristics and Severity of Liver Disease.

BACKGROUND: Prolonged time on the waiting list affects post-transplant survival of patients with hepatocellular carcinoma (HCC). However, it is not yet known which patients will be at higher risk for early dropout from the list. We investigate specific risk factors for early waiting list dropout in patients with HCC. METHODS: This was a single-center, intention-to-treat analysis of adults with HCC, within the Milan criteria, from July 2006 through September 2013. Patients were divided into groups according to waiting list time. The main end point was dropout from the list. RESULTS: The dropout rates of the study cohort at 3, 6, and 12-months were 6.4%, 12.4%, and 17.7%, respectively. Patients who dropped out from the list tended to be older, with blood types A and O, and with higher Child-Pugh and Model for End-Stage Liver Disease (MELD) scores. They also had larger nodules, responded poorly to trans-arterial chemo-embolization (TACE), and had a higher alpha-fetoprotein. Those with blood types B and AB appeared to be protected for dropout (odds ratio [OR] = 0.21, P = .02). Patients who responded to TACE were also protected (OR = 0.22, P < .001). When we looked into time to dropout, the only baseline characteristic that stood out was a higher MELD score (13 for those dropping out up to 90 days vs 10 for those dropping out after 180 days, P = .0025). CONCLUSIONS: We conclude that patients who drop out early from the list are primarily driven by the severity of liver disease. Patients who had progressive HCC had a high tumor load and poor response to loco-regional therapies, dropping out from the list after 180 days of inclusion.

Alpha-ketoisocaproate increases the in vitro 32P incorporation into intermediate filaments in cerebral cortex of rats.

In this study we investigated the effects of alpha-ketoisocaproic (KIC), alpha-ketoisovaleric (KIV) and alpha-keto-beta-methylvaleric (KMV) acids on the phosphorylation of intermediate filament (IF) proteins of cerebral cortex of rats. Tissue slices were incubated with [32P] orthophosphate in the presence or absence of the acids. The intermediate filament enriched cytoskeletal fraction was isolated and the radioactivity incorporated into neurofilament subunits, vimentin and glial fibrillary acidic protein was measured. Results demonstrated that KIC significantly increased phosphorylation of these proteins whereas the other acids had no effect. Experiments using protein kinase inhibitors indicated that the effect of KIC was mediated by Ca2+/calmodulin- and cAMP-dependent protein kinases. This study provides evidence that KIC, a key metabolite accumulating in maple syrup urine disease, increases phosphorylation of IF proteins.

Methylmalonic and propionic acids increase the in vitro incorporation of 32P into cytoskeletal proteins from cerebral cortex of young rats through NMDA glutamate receptors.

In this study we investigated the effects of methylmalonic acid (MMA) and propionic acid (PA) on the phosphorylation of cytoskeletal proteins of cerebral cortex of rats. Slices of tissue were incubated with 32P-orthophosphate in the presence or absence of glutamate, MMA, PA and ionotropic or metabotropic glutamate receptor agonists. The cytoskeletal fraction was isolated and the radioactivity incorporated into the cytoskeletal proteins was measured. Results demonstrated that the acids, glutamate and NMDA increased the phosphorylation of the proteins studied. However, this effect was not observed for non-NMDA ionotropic agonists or metabotropic agonists. Experiments using glutamate receptor antagonists confirmed that MMA and PA at the same concentrations as found in tissues from propionic or methylmalonic acidemic children increase the phosphorylation of cytoskeletal proteins, possibly via NMDA glutamate receptors. Therefore, it is feasible that these findings may be related to the neurological dysfunction characteristic of these disorders.

Acute effects of ethanol and ethanol plus furosemide on pancreatic capillary blood flow in rats.

The effects of intravenous ethanol and ethanol plus furosemide on pancreatic capillary blood flow (PCBF) were investigated using a laser-Doppler flowmeter. Forty Sprague-Dawley male rats were divided into 4 groups: (1) control, (2) 80% ethanol, (3) 80% ethanol plus furosemide, and (4) furosemide. Mean arterial blood pressure and heart rate were monitored. Levels of serum amylase, calcium, electrolytes, ethanol, and furosemide (groups 3 and 4) were measured, and samples of pancreatic tissue were obtained. The ethanol and furosemide levels were statistically different (p < 0.05). PCBF significantly decreased (p < 0.05) in group 2, increased (p < 0.05) in group 3, and did not differ (p > 0.05) between groups 1 and 4. Histopathologic analysis revealed swollen acini in group 2 and sparse focal necrosis without acinar swelling in group 3. The depressant effect of ethanol on PCBF may be the result of its direct action on pancreatic cells causing edema and capillary compression rather than on primary vascular control mechanisms that adjust blood flow. Furosemide counters this effect.

Autoimmune keratolysis in a patient with leukocytoclastic vasculitis: unusual erythema elevatum diutinum with granulomatous pattern.

PURPOSE: Leukocytoclastic vasculitis (LCCV) is an immune complex-mediated, small vessel disease that is clinically characterized by the presence of palpable purpuric lesions, most often in association with rheumatic diseases. Ocular manifestations of LCCV are rare. METHODS: We describe a patient with an unusual granulomatous pattern of erythema elevatum diutinum (EED) associated with autoimmune keratolysis. RESULTS: We studied a 64-year-old man with decreased visual acuity and nodular lesions in both hands. Ocular examination revealed bilateral superior corneal melting with perforation in the left eye and conjunctival thickening in both eyes, in association with a severe inflammatory reaction. Histopathologic examination of the conjunctiva revealed granulomatous vasculitis with neutrophilic infiltrate, giant cells, and fibroblastic proliferation. A punch biopsy taken from his skin showed similar characteristics that suggested EED; however, there were no giant cells. CONCLUSION: To our knowledge, autoimmune keratolysis secondary to cutaneous LCCV (EED) has not been described previously, and there has been no description of granulomatous reaction (in the conjunctiva) in EED.

Hemorrhagic ascites associated with endometriosis. A case report.

BACKGROUND: Endometriosis associated with massive, bloody ascites is an unusual occurrence. This report draws attention to this condition as a complication of endometriosis, with the description of a case and a review of 31 others. CASE: A 41-year-old, black nulligravida with massive, bloody ascites and a pelvic mass underwent laparotomy, and an intraoperative microscopic examination ruled out malignancy. The histologic report was compatible with endometriosis. The patient was treated with a GnRH analog, with progressive reduction of ascitic fluid and full remission after six months. CONCLUSION: Bloody ascites should be considered a complication of endometriosis, especially in nulliparous women of childbearing age with abdominal distention, a pelvic mass, dysmenorrhea, abdominal pain, weight loss and eventual pleural effusion, suggesting a diagnosis of ovarian malignancy.

Ultrastructure of the salivary glands of Rhodnius domesticus Neiva & Pinto, 1923 (Hemiptera: Reduviidae).

The fine structure of the salivary glands of the triatomine bug Rhodnius domesticus was investigated. Stereomicroscopy and scanning electron microscopy showed that each salivary gland pair contains two close and independent units: the larger is reddish and elongated (principal gland), while the smaller is round and translucent (accessory gland). The accessory gland opens at the base of the main excretion duct, which arises at the medial portion of the principal gland. An accessory duct emerges at the base of the main excretion duct, above the accessory gland opening, and runs towards the digestive tract. Transmission electron microscopy showed that both gland units are formed by a single layer of epithelial gland cells, surrounded by a thick basal lamina containing tracheolae and muscle cell fibers. Adjacent gland cells are interconnected by interdigitations of their lateral plasma membranes and by septate junctions. Microvilli are present at the apical domain of the gland cell plasma membrane, which allow faster diffusion of the saliva towards the gland lumen. Several mitochondria, abundant endoplasmic reticulum profiles and usually one elongated nucleus are observed in the gland cells. According to standard nomenclatures, the salivary gland cells can be classified as type I cells, secreting the saliva into a large gland lumen.

Response to transarterial chemoembolization in candidates with hepatocellular carcinoma within Milan criteria does not predict post-transplant disease-free survival.

INTRODUCTION: Few groups have studied the impact of pretransplant transarterial chemoembolization (TACE) in the outcomes of liver transplant recipients with hepatocellular carcinoma (HCC). We verified whether response to TACE in HCC candidates impacts post-transplant disease-free survival. METHODS: This a single center retrospective study of patients who underwent liver transplantation from 2006-2013. Included were those transplanted due to HCC within the Milan criteria who were treated with TACE in the pre-transplant period. Response to TACE followed the modified RECIST (mRECIST) criteria. Disease free-survival was the main endpoint of the study. RESULTS: We included 187 patients in this study. The population had an average age of 57.5 years, predominantly formed by men (82.5%), with an average IMC of 26.7, MELD of 13, with viral hepatitis as main cause of liver disease. Average waiting time was 253 days and follow-up was 27.3 months. Based on response to TACE, 3-year disease-free survival was 84.1% for those with complete response to TACE, 84.1% for those with partial response to TACE, 85.7% for those with stable disease and 100% for patients with progressive disease. Multivariate analysis did not identify response to TACE as a predictor of disease-free post-transplant survival. CONCLUSIONS: Response to TACE in candidates with HCC within Milan criteria does not predict post-transplant disease-free survival.

The potential role of increased adrenal volume in the pathophysiology of obesity-related type 2 diabetes.

The hypothalamic-pituitary-adrenal (HPA) axis seems to play an important role in obesity and Type 2 diabetes (DM). The aim of the present study was to determine the adrenal volume in obese patients with DM in comparison to obese non-diabetic patients. Eleven diabetic obese and 19 non-diabetic obese women were sequentially invited to take part in the study. Computed tomography (CT) scan of the abdomen was performed to determine adrenal volume, visceral (VF) and sc fat (SCF). Daily urinary free cortisol (UFC) was used as a measure of integrated cortisol production. In the diabetic patients, hemoglobin A1c was measured as an index of metabolic control. Compared to nondiabetic controls, patients with diabetes had a significantly higher total adrenal volume (4.29+/-1.50 vs 2.95+/-1.64; p=0.03). A highly significant correlation was detected between VF and VF/SCF ratio and total adrenal volume in the whole group (r=0.36, p=0.04 and r=0.48, p=0.008, respectively). This study, therefore, suggests an association between abdominal obesity, enlarged adrenals and Type 2 diabetes. These findings support the hypothesis that an increased activity of the HPA axis in obese subjects may be involved in the pathogenesis of Type 2 diabetes.

Benzoyl-L-arginine methyl ester (BAME)-esterase activity in human plasma during the gravidic-puerperal cycle.

Benzoyl-L-arginine methyl ester (BAME)-esterase activity of plasma was measured in women going through the gravidic-puerperal cycle and compared with plasma of non-pregnant women. Plasma from women in the 36th to 40th week of pregnancy hydrolyzes BAME two times more rapidly than that from non-pregnant women. During pregnancy, BAME-esterase activity in plasma increases progressively up to the 40th week, decreases during labor, and after delivery reaches the same level as in non-pregnant women. The BAME-esterase activity of plasma was affected by the storage temperature, with differences demonstrable between -20 and -4 C and between pregnant and non-pregnant women.

[Materno-fetal acid-base equilibrium evaluation in parturients submitted to ketamine anesthesia (author's transl)]. / Avaliação do equilíbrio ácido-básico materno e fetal em parturientes submetidas a anestesia pela ketamina

In the present work ketamine was used as anesthetic during the labor in order to evaluate the effect of this anesthetic on the binominal fetus-mother. Two groups of parturients and their fetuses, were studied: 1) The experimental group, with 22 parturients and their fetuses submitted to ketamine anesthesia during the labord, and 2) The control group, with 20 parturients and their fetuses without any analgesic treatment during the labor. In 20 cases of the experimental group the anesthetic was injected during the delivery labor and the other two just before it. It were evaluated in the mother's blood the biochemical parameters of the acid-base balance and others collateral effects of the anesthesia; on the fetus's side the same parameters also and the cardiac frequency. The newborn were evaluated by Apgar Score during the first and fifth minutes of life. The incidence of the spontaneous delivery in the experimental group, was 78%; in 22% of these patients the forceps of relief was used. In 22 cases in which Ketamine was applied it were observed, the following events: elevation of the blood pressure (50%), perineum rigidness (18%), dreams and or hallucinations (18%), increase of the cardiac frequency (9%), apneia (4%) and nausea (4%). It was also observed an increase of uterine tonus an abolishment of abdominal press during the delivery labor, studied through the uterine electromyography register. It was noted after the Ketamine application a fall in the pH of the maternal peripherical venous blood, fetal skull blood and the pH of the blood of the umbilical vein. 22% of the newborns, from the experimental group, presented a depression in the first minute of life (Apgar less than or equals to 6). The pCO2 values in the blood of the umbilical artery were higher in the experimental group than in the control one.

[BAME-Esterase activity in plasmas from blood of human placental interveillous space and umbilical cord vessels (author's transl)]. / Actividad BAME-esterásica en los plasmas de la sangre del espacio intervelloso de la placenta humana y de los vasos del cordón umbilical.

The authors studied an enzymatic activity (BAME-esterase) from human plasma, intimately related with the bradykinin release mechanisms. The optimal conditions of evaluation of the different plasmas were determined. Lately, the authors showed the results obtained with plasma from maternal peripheral blood, umbilical vessels blood and human placental intervillous space blood. It was concluded: 1. The study of enzymatic kinetics allows to establish a reaction time of 30 minutes, and the enzymatic concentration contained within 0.5 ml. of plasma, as ideal parameters to determine the enzymatic activities into the different compartments. 2. In the cases studied, considered clinically normals, the enzymatic activity in plasma from the interveillous space, before and after the detachment of the placenta, was greater than in peripheral maternal and umbilical vessels bloods. The activity in umbilical artery plasma was greater than in umbilical vein and practically the same as in maternal plasma. 3. The esterase activity values into the compartments studied in pre-eclamptics, were similar to that found in the cases considered clinically normal.

Effects of maternal and fetal plasma from toxemic patients on the vasomotility of the human umbilical artery.

Maternal and fetal plasmas from patients with specific hypertensive disease of pregnancy (SHDP) are shown to have a greater vasoconstrictive effect on perfused human unbilical artery than plasma from normal parturients. The vasomotility of isolated segments of artery was determined by measuring perfusion pressure at constant flow rate. The differences were demonstrable with plasmas and artery segments from the same parturients and also when plasma from patients with SHDP and arteries from normal parturients were used. These results, which show that plasmas from SHDP patients have a larger vasoconstrictive effect on human umbilical artery than normal plasma, support and extend the suggestion that there may be humoral mechanism which participates in the physiopathology of SHDP. This humoral factor can be detected with human umbilical artery from both normal and SHDP parturients.

Estriol reduces the reactivity of the human umbilical artery to mechanical stimuli.

The effect of estriol on the reactivity of the human umbilical artery to mechanical stimulation was studied using an in vitro perfusion method. The mechanical stimuli were produced by force applied to the outer surface of the vessel through a system consisting of a lever with equal length arms which was activated by small weights of known mass placed on one of the arms. The contractions of the preparations were proportional to the weights applied. When a 0.5-gram stimulus was applied, the mean contractile response of seven preparations was 46.7 +/- 2.72 mm Hg (mean +/- SEM). The addition of 10 micrograms/ml estriol to the nutrient fluid (Tyrode) caused a (mean 6.8 +/- 1.32 mm Hg) reduction of the response to the mechanical stimuli. We suggest that estrogens, and estriol in particular, play an important role in the modulation of the reactivity of the human umbilical artery during pregnancy in the presence of the mechanical stimulation caused by intrauterine fetal movements.

Estriol antagonism of the action of bradykinin and adrenalin on human umbilical artery.

The effect of estriol on the response of human umbilical artery to bradykinin (0.2 microgram/ml) and adrenalin (0.8 microgram/ml) was studied by an in vitro perfusion method. Estriol (10 microgram/ml) added to the nutrient medium decreased the response of the preparation to the two vasoactive agents. The results suggest the participation of estriol as a modulator of the vascular response at the level of the umbilical circulation, where it may act to protect the maternal-fetal circulatory system from physical or chemical stimuli.

Vasodilating effect of estrogen on the human umbilical artery.

The effects of estradiol, estrone and estriol on the tonus of the isolated vascular segments of human umbilical artery were studied by a perfusion technique. Estradiol (10 microgram/ml), estrone (10 microgram/ml) or estriol (2 and 10 microgram/ml) produce relaxation of the vascular bed which was reflected in a significant reduction in basal pressure of segments perfused at constant rate. A dose-dependent relationship was demonstrated for estriol. The time dependence and extent of relation were similar for all three natural estrogens.