Does pregabalin act in pain control after lateral pharyngoplasties and tonsillectomies? A pilot study.

OBJECTIVE: Some studies have pointed to gabapentinoids as promising medications in postoperative pain control. The objective of the present study was to evaluate the efficacy of pregabalin in reducing postoperative pain in tonsillectomy and lateral pharyngoplasties. STUDY DESIGN: Double-blind randomized controlled trial. SETTING: Tertiary care center. METHODS: A double-blind randomized controlled trial was conducted with patients undergoing tonsillectomies and lateral pharyngoplasties between Aug 29, 2017, and Oct 31, 2020. Data of interest such as opioid consumption, pain scores, and adverse outcomes such as dizziness, nausea, headache, and sedation within 7 days following surgeries were analyzed. RESULTS: No statistically significant difference was observed in pain scores and opioid consumption between the groups studied in the pilot project. The use of pregabalin was associated with lower incidence of dizziness compared to controls. CONCLUSION: Gabapentinoids, especially pregabalin, are drugs whose potential for controlling pain after pharyngeal surgery, such as tonsillectomy and sleep apnea surgery, still needs to be more fully evaluated. After the conclusion of the present study, we hope to answer this question about the role of pregabalin in oropharyngeal surgeries.

Oral fish oil positively influences nutritional-inflammatory risk in patients with haematological malignancies during chemotherapy with an impact on long-term survival: a randomised clinical trial.

BACKGROUND: Studies suggest that the ingestion of fish oil (FO), a source of the omega-3 polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), can reduce the deleterious side-effects of chemotherapy. The aim of this randomised clinical trial was to evaluate the effect of supplementation with oral FO for 9 weeks on nutritional parameters and inflammatory nutritional risk in patients with haematological malignancies during the beginning of chemotherapy. METHODS: Twenty-two patients with leukaemia or lymphoma were randomised to the unsupplemented group (UG) (n = 13) or supplemented group (SG) (n = 9). SG received 2 g/day of fish oil for 9 weeks. Nutritional status, serum acute-phase proteins and plasma fatty acids were evaluated before (T0) and after (T1) the intervention period. Data were analysed using two models; model 1, comprising data from all patients included in the study, and model 2, comprising data from UG patients with no increase in the proportions of EPA and DHA in plasma and data from SG patients showing an at least 100% increase in plasma EPA and DHA. RESULTS: SG showed an increased plasma proportion of EPA and DHA in both models. In model 2, C-reactive protein (CRP) and CRP/albumin ratio showed larger reductions in the SG. Overall long-term survival in both models (465 days after the start of the chemotherapy) was higher in the group ingesting fish oil (P < 0.05). CONCLUSIONS: These findings indicate an improved nutritional-inflammatory risk and potential effects on long-term survival in patients with haematological malignancies supplemented with FO during the beginning of chemotherapy.

Hiatal hernia and gastroesophageal reflux: Study of collagen in the phrenoesophageal ligament.

BACKGROUND: Gastroesophageal reflux disease (GERD) is defined by the intensity and/or quality of the reflux of gastric or duodenal contents into the esophagus. Surgical treatment of GERD has shown conflicting results and unacceptable recurrence rates, mainly due to herniation of the antireflux valve into the chest. A variety of techniques has been proposed to reduce GERD recurrence, including routine use of prosthesis in cruroplasty. The prevalence of GERD in patients with hiatal hernia (HH) can reach 94 %. It is possible that the phrenoesophageal ligament (POL) engaged in the stabilization of the gastroesophageal junction in the abdomen may be an etiological factor of HH. We conducted a study to evaluate collagen in the constitution of the POL in patients with HH and cadavers without HH. METHODS: POL samples were collected from 29 patients with HH and GERD (cases) and 32 samples from cadavers without HH (controls). Total collagen was quantified through the Picrosirius red histochemical technique, and type-I and type-III collagens were quantified immunohistochemically using a monoclonal antibody. The stained slides were photographed, and images were quantified by computer software (Image Pro Plus) to count the pixels per field. RESULTS: The mean age was 49.5 (±11.5) years for the cases and 38.5 (±13) years for the controls (p < 0.01). Seventeen cases (58.6 %) and six controls (18.75 %) were female (p < 0.01). The quantity of total (p < 0.01), type-I (p < 0.01), and type-III (p < 0.05) collagens was significantly lower by about 60 % in patients with HH compared with controls. CONCLUSION: Our data indicate that the composition of POL for patients with GERD and HH includes less total, type-I, and type-III collagens than that of the POL of cadavers without HH. The quality of the POL may be an etiological factor in the development of HH.

A pediatric case of gluten sensitivity with severe neurological presentation.

UNLABELLED: Neurologic manifestations are present in a reasonable proportion of adult celiac patients and can be the first sign of gluten sensitivity. In children, the risk of neurological complications is lower, and gluten sensitivity with neurological presentation seems to be rare. We report a case of gluten sensitivity with severe neurological presentation in a 3-year-old girl. In the absence of gastrointestinal symptoms, the presence of white matter lesions in cerebral magnetic resonance imaging suggested an acute disseminated encephalomyelitis. Recurrence of neurologic symptoms and cerebral lesions over a long period of time made the authors consider an autoimmune/inflammatory systemic disease. IgA anti-transglutaminase (TG) 2 was elevated and duodenal biopsy confirmed the presence of enteropathy. A gluten-free diet led to complete resolution of neurological manifestations and arrest of white matter lesions progression. CONCLUSION: In children with unclear neurologic manifestations with probable autoimmune etiology, anti-TG2 autoantibody titers should be determined considering the possibility of gluten sensitivity. Gluten-free diet remains the only effective treatment reported to date and, therefore, should be recommended to all patients with gluten sensitivity despite the type of manifestations. More studies, focusing on neurological manifestations and its response to gluten-free diet, are needed.

[Outcome of laparoscopic Heller myotomy in children]. / Miotomía de Heller laparoscópica: resultados en niños.

AIM: The appropriate management of achalasia in children remains debatable. The present study aimed to evaluate the outcome of laparoscopic Heller myotomy by assessing short- and mid-term issues. METHODS: Children submitted to surgery from 2002 to 2010 were included. Surgery was proposed after failure of endoscopic dilatations. All patients underwent esophagocardiomyotomy (Heller) plus anterior fundoplication (Dor) by laparoscopy. Demographics, presentation symptoms and perioperative details were analyzed. The outcomes were assessed both by medical records and the application of a 14 items (score 0-worst to 4-best/normal) self-evaluation questionnaire (modified GIQLI - covering only upper gastrointestinal symptoms). RESULTS: Six patients (5 males) with a median age of 12.2 years (range: 0.8-14.2) were submitted to surgery. The presenting symptoms were: dysphagia (83.3%), weight loss (50%), vomiting (33.3%), chronic cough (33.3%), and chest pain (16.7%). All patients were operated on by laparoscopy with no conversions; there were no intra or postoperative complications. At a median follow-up of 5 years (range: 2-10) none of the patients were re-operated. Five patients have normal eating habits; the remaining case presented recurrent episodes of dysphagia requiring regular endoscopic dilatations (every 6 months). The total GIQLI presented a mean score of 49.3 (range, 45-52) representing 88.1% of the theoretical maximum. The score for frequency of dysphagia episodes was 1.6 +/- 1.4; all patients scored 3 for the grade of dysphagia. CONCLUSIONS: Laparoscopic Heller myotomy is effective and safe for achalasia in children, offering a good and durable quality of life; although frequent, the dysphagia episodes were mild.

Skin manifestations of obesity: a comparative study.

BACKGROUND: Obesity is one of the world's biggest health problems nowadays. Little research has been done on the skin diseases that affect obese patients. OBJECTIVE: To study the prevalence of skin manifestations in obese patients compared with a control group of normal-weight patients. METHODS: A total of 76 obese patients [body mass index (BMI) ≥30 kg/m(2) ] and 73 with normal-weight volunteers (BMI 18.5-24.9 kg/m(2) ) were included in the study and had their complete medical history and skin examination evaluated by the same examiner. All patients were investigated for the presence of metabolic syndrome. RESULTS: The dermatoses that showed a statistically significant relationship with obesity, compared with the control group were: striae (P < 0.001), plantar hyperkeratosis (P < 0.001), acrochordons (P = 0.007), intertrigo (P < 0.001), pseudoacanthosis nigricans (P < 0.001), keratosis pilaris (P = 0.006), lymphedema (P = 0.002) and bacterial infections (P = 0.05). The presence of striae, pseudoacanthosis nigricans and bacterial infections were also found to be correlated with the degree of obesity. CONCLUSIONS: Obesity is strongly related to several skin alterations that could be considered as markers of excessive weight. Skin care of obese patients deserves particular attention, not only because of the high prevalence of cutaneous alteration but mainly because many of these disorders are preventable and could be treated, improving patient's quality of life.

Green does not always mean go: A sulfated galactan from Codium isthmocladum green seaweed reduces melanoma metastasis through direct regulation of malignancy features.

Melanoma is the most lethal form of skin cancer, with a worldwide increase in incidence. Despite the increased overall survival of metastatic melanoma patients given recent advances in targeted and immunotherapy, it still has a poor prognosis and available treatment options carry diverse severe side effects. Polysaccharides from seaweed have been shown to exert antitumor activities. Here we show in vitro and in vivo antitumor activities of a sulfated homogalactan (named 3G4S) from Codium isthmocladum seaweed in the B16-F10 murine melanoma cell line. 3G4S did not induce cytotoxicity or proliferation changes; however, it was able to reduce solid tumor growth and metastasis, while not inducing side effects in mice. B16-F10 cells traits related to the metastatic cascade were also impaired by 3G4S, reducing cell invasion, colony-forming capacity and membrane glycoconjugates. Therefore, 3G4S shows promising antitumor activities without the commonly associated drawbacks of cancer treatments and can be further explored.

Non-Cytotoxic Sulfated Heterorhamnan from Gayralia brasiliensis Green Seaweed Reduces Driver Features of Melanoma Metastatic Progression.

Melanoma is a form of skin cancer with high mortality owing to its fast progression and metastatic capacity. The treatments available nowadays are only palliative in advanced stages of the disease. Thus, alternative therapies for cancer treatment are in demand, and molecules from natural sources, such as polysaccharides, could represent new possible therapeutic approaches. Polysaccharides of freshwater and marine algae with biological activities, such as antitumor properties, are greatly reported in the scientific literature. In the present study, a sulfated heterorhamnan obtained from the green seaweed Gayralia brasiliensis (Gb1 fraction) was chemically characterized and its biological activities in the B16-F10 murine melanoma cell line were evaluated. The Gb1 polysaccharidic fraction tested concentrations presented low or absence of cytotoxicity to B16-F10 cells and neither cell proliferation nor cell cycle were altered. Interestingly, Gb1 treatment decreased B16-F10 cells migration and invasion capabilities and CD44 labeling, showing to be a promising compound for further in vitro and in vivo antitumor studies.

Acute gastric dilatation and necrosis: a case report.

Massive gastric dilatation with necrosis and rupture is a very rare event. Here we describe the case of a 13-year-old girl with acute gastric dilatation, infarction, necrosis and perforation. It began with acute abdominal pain, but an absence of vomiting after eating a heavy meal. Laparotomy showed massive gastric dilatation with infarction and perforation. Early diagnosis is essential to reduce morbidity and mortality, and therefore treatment must be started promptly.

Malignancy and mortality in paediatric-onset inflammatory bowel disease: a 3-year prospective, multinational study from the paediatric IBD Porto group of ESPGHAN.

BACKGROUND: Risk benefit strategies in managing inflammatory bowel diseases (IBD) are dependent upon understanding the risks of uncontrolled inflammation vs those of treatments. Malignancy and mortality in IBD have been associated with disease-related inflammation and immune suppression, but data are limited due to their rare occurrence. AIM: To identify and describe the most common causes of mortality, types of cancer and previous or current therapy among children and young adults with paediatric-onset IBD. METHODS: Information on paediatric-onset IBD patients diagnosed with malignancy or mortality was prospectively collected via a survey in 25 countries over a 42-month period. Patients were included if death or malignancy occurred after IBD diagnosis but before the age of 26 years. RESULTS: In total, 60 patients were identified including 43 malignancies and 26 fatal cases (9 due to cancer). Main causes of fatality were malignancies (n = 9), IBD or IBD-therapy related nonmalignant causes (n = 10; including 5 infections), and suicides (n = 3). Three cases, all fatal, of hepatosplenic T-cell lymphoma were identified, all were biologic-naïve but thiopurine-exposed. No other haematological malignancies were fatal. The 6 other fatal cancer cases included 3 colorectal adenocarcinomas and 3 cholangiocarcinomas (CCAs). Primary sclerosing cholangitis (PSC) was present in 5 (56%) fatal cancers (1 colorectal carcinoma, 3 CCAs and 1 hepatosplenic T-cell lymphoma). CONCLUSIONS: We report the largest number of paediatric-onset IBD patients with cancer and/or fatal outcomes to date. Malignancies followed by infections were the major causes of mortality. We identified PSC as a significant risk factor for cancer-associated mortality. Disease-related adenocarcinomas were a commoner cause of death than lymphomas.

Laparoscopic excision of a retroperitoneal cystic lymphangioma in an elderly patient.

A 68-year-old male patient was referred to our hospital due to protrusion and pain in the right iliac fossa. On physical examination a palpable oval tumor was found. Ultrasonography and computed tomography revealed a cystic mass in right iliac fossa. The tumor was successfully excised laparoscopically and histologically diagnosed as cystic lymphangioma. Retroperitoneal cystic lymphangiomas are rare lesions, most often seen in pediatric patients. Surgical excision is the treatment of choice because of its potential to grow and develop complications, especially due to mass effect. The laparoscopic approach is a safe and effective alternative for treatment of retroperitoneal cystic lymphangioma in the elderly.

Safe therapeutics of murine melanoma model using a novel antineoplasic, the partially methylated mannogalactan from Pleurotus eryngii.

A heteropolysaccharide was isolated by cold aqueous extraction from edible mushroom Pleurotus eryngii ("King Oyster") basidiocarps and its biological properties were evaluated. Structural assignments were carried out using mono- and bidimensional NMR spectroscopy, monosaccharide composition, and methylation analyses. A mannogalactan having a main chain of (1→6)-linked α-d-galactopyranosyl and 3-O-methyl-α-d-galactopyranosyl residues, both partially substituted at OH-2 by ß-d-Manp (MG-Pe) single-unit was found. Biological effects of mannogalactan from P. eryngii (MG-Pe) were tested against murine melanoma cells. MG-Pe was non-cytotoxic, but reduced in vitro melanoma cells invasion. Also, 50mg/kg MG-Pe administration to melanoma-bearing C57BL/6 mice up to 10days decreased in 60% the tumor volume compared to control. Additionally, no changes were observed when biochemical profile, complete blood cells count (CBC), organs, and body weight were analyzed. Mg-Pe was shown to be a promising anti-melanoma molecule capable of switching melanoma cells to a non-invasive phenotype with no toxicity to melanoma-bearing mice.

Bjcul, a snake venom lectin, modulates monocyte-derived macrophages to a pro-inflammatory profile in vitro.

Macrophages are cells of high plasticity and can act in different ways to ensure that the appropriate immune response remains controlled. This study shows the effects of the C-type Bothrops jararacussu venom lectin (BJcuL) on the activation of human macrophages derived from the U937 cell line. BJcuL binds on the cell surface, and this event is inhibited by its specific carbohydrate. It induced phagocytosis and production of H2O2, and expression of antigen presentation molecules. It also enhanced the production of TNF-α, GM-CSF and IL-6 by macrophages and indirectly induced T cells to an increased production of TNF-α, IFN-γ and IL-6 in the presence of LPS. Our results suggest that BJcuL can modulate macrophage functional activation towards an M1 state.

Evaluation of L1 and L2 minimum norm performances on EEG localizations.

OBJECTIVE: In this work we study the performance of minimum norm methods to estimate the localization of brain electrical activity. These methods are based on the simplest forms of L(1) and L(2) norm estimates and are applied to simulated EEG data. The influence of several factors like the number of electrodes, grid density, head model, the number and depth of the sources and noise levels was taken into account. The main objective of the study is to give information about the dependence, on these factors, of the localization sources, to allow for proper interpretation of the data obtained in real EEG records. METHODS: For the tests we used simulated dipoles and compared the localizations predicted by the L(1) and L(2) norms with the location of these point-like sources. We varied each parameter separately and evaluated the results. RESULTS: From this work we conclude that, the grid should be constructed with approximately 650 points, so that the information about the orientation of the sources is preserved, especially for L(2) norm estimates; in favorable noise conditions, both L(1) and L(2) norm approaches are able to distinguish between more than one point-like sources. CONCLUSIONS: The critical dependence of the results on the noise level and source depth indicates that regularized and weighted solutions should be used. Finally, all these results are valid both for spherical and for realistic head models.

Heparin and a cyclic octaphenol-octasulfonic acid (GL-522-Y-1) bind with high affinity to a 47-kda protein from vascular endothelial cell surface and stimulate the synthesis and structural changes of heparan sulfate proteoglycan.

The effect of a cyclic octaphenol-octasulfonic acid (GL-522-Y-1), upon the synthesis of a heparan sulfate proteoglycan synthesized by endothelial cells (rabbit aorta and human umbilical vein) were studied. The cells were exposed to the compounds at various concentrations for different periods of time and the synthesized heparan sulfates analyzed by a combination of agarose gel electrophoresis and enzymatic degradation. The GL-522-Y-1, like heparin, change the sulfation pattern and stimulate two- to three-fold the synthesis of heparan sulfate proteoglycan secreted by rabbit and human endothelial cells in culture. GL-522-Y-1, besides being 100 times more active than heparin, also produces a significant enhancement of cell surface heparan sulfate in human vein endothelial cells. The effect of GL-522-Y-1 is completely abolished by methylation or acetylation of its free hydroxyl groups. Both heparin and GL-522-Y-1 have high affinity for a 47-kDa protein present at the surface of endothelial cells. These and other results lead us to speculate that the antithrombotic activity of heparin and GL522 "in vivo" could be related, at least in part, to the increased production of the heparan sulfate proteoglycan by endothelial cells.

In vivo and in vitro cytotoxicity of brown spider venom for blood vessel endothelial cells.

The effect of brown spider (Loxosceles intermedia) venom on endothelial cells was investigated in vivo and in vitro. Morphological and ultrastructural observations by light microscopy and transmission electron microscopy showed that the venom acts in vivo upon vessel endothelial cells of rabbits that were intradermally injected, evoking vessel instability, cytoplasmic endothelial cell vacuolization, and blebs. Likewise, treatment of rabbit endothelial cells in culture with the venom led to loss of adhesion of the cells to the substrate. Endothelial cells in culture were metabolically radiolabeled with sodium [35S]-sulfate and the sulfated compounds (proteoglycans and sulfated proteins) from medium, cell surface, and extracellular matrix (ECM) were analyzed. Agarose gel electrophoresis and SDS-PAGE showed that the venom is active on the ECM and on cell surface proteoglycans, shedding these molecules into the culture medium. In addition, when purified heparan sulfate proteoglycan (HSPG) and purified laminin-entactin (LN/ET) complex were incubated with the venom we observed a partial degradation of the protein core of HSPG as well as the hydrolysis of entactin. The above results suggest that the L. intermedia venom has a deleterious effect on the endothelium of vessels both in vivo and in culture, removing important constituents such as HSPG and entactin that are involved in the adhesion of endothelial cells and of subendothelial ECM organization.

Heparan sulfate and control of cell division: adhesion and proliferation of mutant CHO-745 cells lacking xylosyl transferase.

We have examined the role of cell surface glycosaminoglycans in cell division: adhesion and proliferation of Chinese hamster ovary (CHO) cells. We used both wild-type (CHO-K1) cells and a mutant (CHO-745) which is deficient in the synthesis of proteoglycans due to lack of activity of xylosyl transferase. Using different amounts of wild-type and mutant cells, little adhesion was observed in the presence of laminin and type I collagen. However, when fibronectin or vitronectin was used as substrate, there was an enhancement in the adhesion of wild-type and mutant cells. Only CHO-K1 cells showed a time-dependent adhesion on type IV collagen. These results suggest that the two cell lines present different adhesive profiles. Several lines of experimental evidence suggest that heparan sulfate proteoglycans play a role in cell adhesion as positive modulators of cell proliferation and as key participants in the process of cell division. Proliferation and cell cycle assays clearly demonstrate that a decrease in the amount of glycosaminoglycans does not inhibit the proliferation of mutant CHO-745 cells when compared to the wild type CHO-K1, in agreement with the findings that both CHO-K1 and CHO-745 cells take 8 h to enter the S phase.

A fucan from the brown seaweed Spatoglossum schröederi inhibits Chinese hamster ovary cell adhesion to several extracellular matrix proteins.

Fucans, a family of sulfated polysaccharides present in brown seaweed, have several biological activities. Their use as drugs would offer the advantage of no potential risk of contamination with viruses or particles such as prions. A fucan prepared from Spatoglossum schröederi was tested as a possible inhibitor of cell-matrix interactions using wild-type Chinese hamster ovary cells (CHO-K1) and the mutant type deficient in xylosyltransferase (CHO-745). The effect of this polymer on adhesion properties with specific extracellular matrix components was studied using several matrix proteins as substrates for cell attachment. Treatment with the polymer inhibited the adhesion of fibronectin to both CHO-K1 (2 x 10(5)) and CHO-745 (2 x 10(5) and 5 x 10(5)) cells. No effect was detected with laminin, using the two cell types. On the other hand, adhesion to vitronectin was inhibited in CHO-K1 cells and adhesion to type I collagen was inhibited in CHO-745 cells. In spite of this inhibition, the fucan did not affect either cell proliferation or cell cycle. These results demonstrate that this polymer is a new anti-adhesive compound with potential pharmacological applications.