Permanent anosmia and ageusia after resection of a left temporoinsular low-grade glioma: anatomofunctional considerations

Five percent of the general population has olfactory or gustatory disorders, although most do not complain about it. However, in some cases, these symptoms can be disabling and may affect quality of life. Anosmia was reported as a possible complication following head injury and neurosurgical procedures, particularly after the resection of tumors located in the anterior fossa and the treatment of aneurysms in the anterior circulation. Nonetheless, in all of these situations, olfactory dysfunction could be explained by damage to the peripheral olfactory system. Here, the authors report a case of complete anosmia associated with ageusia following awake resection of a low-grade glioma involving the left temporoinsular region, with no recovery during a follow-up of 3 years. The frontal lobe was not retracted, and the olfactory tract was not visualized during surgery; therefore, postoperative anosmia and ageusia are likely explained by damage to the cortex and central pathways responsible for these senses. The authors suggest that the patient might have had a subclinical right hemianosmia before surgery, which is a common condition. After resection of the central structures critical for smell and taste processing in the left hemisphere, the patient could have finally had bilateral and complete olfactory and gustatory loss. This is the first known report of permanent anosmia and ageusia following glioma surgery. Because these symptoms might have been underestimated, more attention should be devoted to olfaction and taste, especially with regard to possible subclinical preoperative deficit. (http://thejns.org/doi/abs/10.3171/2012.2.JNS111982)

Terapia nutricional no traumatismo cranioencefálico grave

O objetivo do presente artigo é revisar a literatura e organizar os principais achados, gerando recomendações baseadas nas melhores evidências encontradas relativas à terapia nutricional nos casos de traumatismo cranioencefálico. O traumatismo cranioencefálico permanece uma patologia altamente letal, apesar dos avanços em seu diagnóstico e tratamento. Poucas intervenções terapêuticas tem se mostrado eficazes em melhorar este quadro. Há múltiplas alterações metabólicas e hidroeletrolíticas decorrentes do traumatismo cranioencefálico, caracterizadas por um estado hipermetabólico associado a um intense catabolismo, que levam a necessidades nutricionais específicas. Na literatura atual não há diretrizes específicas para terapia nutricional em pacientes vítimas de traumatismo cranioencefálico grave, mas há muitos dados interessantes e questões que estão sendo melhores estudadas, possibilitando um melhor direcionamento da terapia nutricional neste cenário. Além de avaliação e acompanhamento por uma equipe multiprofissional qualificada e treinada para estas questões, a introdução precoce do suporte nutricional, a utilização preferencial da via enteral com a infusão adequada de calorias, o uso de formulações adequadas e nutricionalmente equilibradas para cada caso específico, associadas a utilização de imunonutrientes específicos, melhor controle hidroeletrolítico e metabólico, além de melhor entendimento fisiopatológico e das consequências das próprias terapêuticas instituídas, parece modificar os desfechos destes casos.

Whole-body computerized tomography and concomitant spine and head injuries A study of 355 cases

The authors present a prospective study on the coexistence of spinal injury (SI) and severe traumatic brain injury (TBI) in patients who were involved in traffic accidents and arrived at the Emergency Department of Hospital das Clinicas of the University of Sao Paulo between September 1, 2003 and December 31, 2009. A whole-body computed tomography was the diagnostic method employed in all cases. Both lesions were observed simultaneously in 69 cases (19.4%), predominantly in males (57 individuals, 82.6%). Cranial injuries included epidural hematoma, acute subdural hematoma, brain contusion, ventricular hemorrhage and traumatic subarachnoid hemorrhage. The transverse processes were the most fragile portion of the vertebrae and were more susceptible to fractures. The seventh cervical vertebra was the most commonly affected segment, with 24 cases (34.78%). The distribution of fractures was similar among the other cervical vertebrae, the first four thoracic vertebrae and the lumbar spine. Neurological deficit secondary to SI was detected in eight individuals (11.59%) and two individuals (2.89%) died. Traumatic subarachnoid hemorrhage was the most common intracranial finding (82.6%). Spinal surgery was necessary in 24 patients (34.78%) and brain surgery in 18 (26%). Four patients (5.79%) underwent cranial and spinal surgeries. The authors conclude that it is necessary a judicious assessment of the entire spine of individuals who presented in coma after suffering a brain injury associated to multisystemic trauma and whole-body CT scan may play a major role in this scenario.

Brainstem injury by penetrating head trauma with a knife

The authors describe a rare case about a traumatic lesion of brain and brain stem with a knife. In this case the patient had good clinical condition, diagnosed with TBI by infectious complications. We have highlighted the unusual diagnosis, proximity of vascular structures, the technique used in the treatment and the good outcome of the injury.

Oxidative Stress and Modification of Renal Vascular Permeability Are Associated with Acute Kidney Injury during P. berghei ANKA Infection

Malaria associated-acute kidney injury (AKI) is associated with 45% of mortality in adult patients hospitalized with severe form of the disease. However, the causes that lead to a framework of malaria-associated AKI are still poorly characterized. Some clinical studies speculate that oxidative stress products, a characteristic of Plasmodium infection, as well as proinflammatory response induced by the parasite are involved in its pathophysiology. Therefore, we aimed to investigate the development of malaria-associated AKI during infection by P. berghei ANKA, with special attention to the role played by the inflammatory response and the involvement of oxidative stress. For that, we took advantage of an experimental model of severe malaria that showed significant changes in the renal pathophysiology to investigate the role of malaria infection in the renal microvascular permeability and tissue injury. Therefore, BALB/c mice were infected with P. berghei ANKA. To assess renal function, creatinine, blood urea nitrogen, and ratio of proteinuria and creatininuria were evaluated. The products of oxidative stress, as well as cytokine profile were quantified in plasma and renal tissue. The change of renal microvascular permeability, tissue hypoxia and cellular apoptosis were also evaluated. Parasite infection resulted in renal dysfunction. Furthermore, we observed increased expression of adhesion molecule, proinflammatory cytokines and products of oxidative stress, associated with a decrease mRNA expression of HO-1 in kidney tissue of infected mice. The measurement of lipoprotein oxidizability also showed a significant increase in plasma of infected animals. Together, our findings support the idea that products of oxidative stress, as well as the immune response against the parasite are crucial to changes in kidney architecture and microvascular endothelial permeability of BALB/c mice infected with P. berghei ANKA.

Decompressive craniectomy and cerebral blood flow regulation in head injured patients: A case studied by perfusion CT

Previous studies have reported increased cerebral blood flow (CBF) velocity after decompressive craniectomy in traumatic brain injury (TBI) patients. A 27-year-old man presented with clinical and tomographic signs of cerebral herniation secondary to TBI. Prior to decompressive craniectomy, hemodynamic study by perfusion computed tomography (CT) indicated diffuse cerebral hyperperfusion. Following surgical decompression, the patient recovered neurologically and perfusion CT disclosed a decrease in the intensity of cerebral perfusion. The patient's blood pressure levels were similar at both pre- and postoperative perfusion CT examinations. This finding provides indirect evidence that decompressive craniectomy may improve mechanisms of CBF regulation in TBI, providing pathophysiological insights in the cerebral hemodynamics of TBI patients. This is the first report analyzing the hemodynamic changes through perfusion CT (PCT) in a patient with decompressive craniotomy due to TBI. (C) 2012 Elsevier Masson SAS. All rights reserved.

Knock out of neuronal nitric oxide synthase exacerbates intestinal ischemia/reperfusion injury in mice

Recent investigation of the intestine following ischemia and reperfusion (I/R) has revealed that nitric oxide synthase (NOS) neurons are more strongly affected than other neuron types. This implies that NO originating from NOS neurons contributes to neuronal damage. However, there is also evidence of the neuroprotective effects of NO. In this study, we compared the effects of I/R on the intestines of neuronal NOS knockout (nNOS(-/-)) mice and wild-type mice. I/R caused histological damage to the mucosa and muscle and infiltration of neutrophils into the external muscle layers. Damage to the mucosa and muscle was more severe and greater infiltration by neutrophils occurred in the first 24 h in nNOS(-/-) mice. Immunohistochemistry for the contractile protein, alpha-smooth muscle actin, was used to evaluate muscle damage. Smooth muscle actin occurred in the majority of smooth muscle cells in the external musculature of normal mice but was absent from most cells and was reduced in the cytoplasm of other cells following I/R. The loss was greater in nNOS(-/-) mice. Basal contractile activity of the longitudinal muscle and contractile responses to nerve stimulation or a muscarinic agonist were reduced in regions subjected to I/R and the effects were greater in nNOS(-/-) mice. Reductions in responsiveness also occurred in regions of operated mice not subjected to I/R. This is attributed to post-operative ileus that is not significantly affected by knockout of nNOS. The results indicate that deleterious effects are greater in regions subjected to I/R in mice lacking nNOS compared with normal mice, implying that NO produced by nNOS has protective effects that outweigh any damaging effect of this free radical produced by enteric neurons.

Tricuspid Valve Injury After Heart Transplantation Due to Endomyocardial Biopsy: An Analysis of 3550 Biopsies

Introduction. Tricuspid regurgitation (TR) is the most commonly valvular dysfunction found after heart transplantation (HTx). It may be related to endomyocardial biopsy (EMB) performed for allograft rejection surveillance. Objective. This investigation evaluated the presence of tricuspid valve tissue fragments obtained during routine EMB performed after HTx and its possible effect on short-term and long-term hemodynamic status. Method. This single-center review included prospectively collected and retrospectively analyzed data. From 1985 to 2010, 417 patients underwent 3550 EMB after HTx. All myocardial specimens were reviewed to identify the presence of tricuspid valve tissue by 2 observers initially and in doubtful cases by a third observer. The echocardiographic and hemodynamic parameters were only considered for valvular functional damage analysis in cases of tricuspid tissue inadvertently removed during EMB. Results. The 417 HTx patients to 3550 EMB, including 17,550 myocardial specimens. Tricuspid valve tissue was observed in 12 (2.9%) patients corresponding to 0.07% of the removed fragments. The echocardiographic and hemodynamic parameters of these patients before versus after the biopsy showed increased TR in 2 cases (2/12; 16.7%) quantified as moderate without progression in the long term. Only the right atrial pressure showed a significant increase (P = .0420) after tricuspid injury; however, the worsening of the functional class was not significant enough in any of the subjects. Thus, surgical intervention was not required. Conclusions. Histological evidence of chordal tissue in EMB specimens is a real-world problem of relatively low frequency. Traumatic tricuspid valve injury due to EMB rarely leads to severe valvular regurgitation; only a minority of patients develop significant clinical symptoms. Hemodynamic and echocardiographic alterations are also less often observed in most patients.

ORAL MUCOSITIS PREVENTION BY LOW-LEVEL LASER THERAPY IN HEAD-AND-NECK CANCER PATIENTS UNDERGOING CONCURRENT CHEMORADIOTHERAPY: A PHASE III RANDOMIZED STUDY

Purpose: Oral mucositis is a major complication of concurrent chemoradiotherapy (CRT) in head-and-neck cancer patients. Low-level laser (LLL) therapy is a promising preventive therapy. We aimed to evaluate the efficacy of LLL therapy to decrease severe oral mucositis and its effect on RT interruptions. Methods and Materials: In the present randomized, double-blind, Phase III study, patients received either gallium-aluminum-arsenide LLL therapy 2.5 J/cm(2) or placebo laser, before each radiation fraction. Eligible patients had to have been diagnosed with squamous cell carcinoma or undifferentiated carcinoma of the oral cavity, pharynx, larynx, or metastases to the neck with an unknown primary site. They were treated with adjuvant or definitive CRT, consisting of conventional RT 60-70 Gy (range, 1.8-2.0 Gy/d, 5 times/wk) and concurrent cisplatin. The primary endpoints were the oral mucositis severity in Weeks 2, 4, and 6 and the number of RT interruptions because of mucositis. The secondary endpoints included patient-reported pain scores. To detect a decrease in the incidence of Grade 3 or 4 oral mucositis from 80% to 50%, we planned to enroll 74 patients. Results: A total of 75 patients were included, and 37 patients received preventive LLL therapy. The mean delivered radiation dose was greater in the patients treated with LLL (69.4 vs. 67.9 Gy, p = .03). During CRT, the number of patients diagnosed with Grade 3 or 4 oral mucositis treated with LLL vs. placebo was 4 vs. 5 (Week 2, p = 1.0), 4 vs. 12 (Week 4, p = .08), and 8 vs. 9 (Week 6, p = 1.0), respectively. More of the patients treated with placebo had RT interruptions because of mucositis (6 vs. 0, p = .02). No difference was detected between the treatment arms in the incidence of severe pain. Conclusions: LLL therapy was not effective in reducing severe oral mucositis, although a marginal benefit could not be excluded. It reduced RT interruptions in these head-and-neck cancer patients, which might translate into improved CRT efficacy. (C) 2012 Elsevier Inc.

Guanylate cyclase inhibition by methylene blue as an option in the treatment of vasoplegia after a severe burn. A medical hypothesis

Today it is known that severe burns can be accompanied by the phenomenon of vasoplegic syndrome (VS), which is manifested by persistent and diffuse vasodilation, hypotension and low vascular resistance, resulting in circulatory and respiratory failure. The decrease in systemic vascular resistance observed in VS is associated with excessive production of nitric oxide (NO). In the last 2 decades, studies have reported promising results from the administration of an NO competitor, methylene blue (MB), which is an inhibitor of the soluble guanylate cyclase (sGC), in the treatment of refractory cases of vasoplegia. This medical hypothesis rationale is focused on the tripod of burns/vasoplegia catecholamine resistant/methylene blue. This article has 3 main objectives: 1) to study the guanylate cyclase inhibition by MB in burns; 2) to suggest MB as a viable, safe and useful co-adjuvant therapeutic tool of fluid resuscitation, and; 3) to suggest MB as burns hypotensive vasoplegia amine-resistant treatment.

Relationship between ozone, meteorological conditions, gas exchange and leaf injury in Nicotiana tabacum Bel-W3 in a sub-tropical region

The city of Sao Paulo is located in a subtropical region whose climate exhibits few defined seasons as well as frequent oscillations in temperature and rainfall throughout the year. In addition to interfering with physiological processes, these peculiar climatic dynamics influence the formation of O-3 and its influx into leaves, causing species used as bioindicators in temperate climates to be ineffective here. This study evaluated gas exchange variations in CO2 and H2O and leaf injuries induced by O-3 in Nicotiana tabacum Bel-W3 in relation to oscillations in environmental conditions. Plants were exposed to an O-3-polluted environment for fifteen periods of fourteen days each throughout 2008. Gas exchange and O-3 were higher during the summer and winter but were highly variable in all seasons. Severe injuries occurred during the winter and spring, with significant variation in this parameter being observed throughout the year. An analysis of biotic and abiotic variables revealed complex relationships among them, with great importance of meteorological factors in plant responses. We conclude that under unstable climatic conditions, the relationship between O-3 flux and injury is weak, and the qualitative character of biomonitoring is further confirmed. (c) 2012 Elsevier Ltd. All rights reserved.

Fetal Pulmonary Response After Fetoscopic Tracheal Occlusion for Severe Isolated Congenital Diaphragmatic Hernia

OBJECTIVE: To estimate the response in lung growth and vascularity after fetal endoscopic tracheal occlusion for severe congenital diaphragmatic hernia in the prediction of neonatal survival. METHODS: Between January 2006 and December 2010, fetal lung parameters (observed-to-expected lung-to-head ratio; observed-to-expected lung volume; and contralateral lung vascularization index) were evaluated before fetal tracheal occlusion and were evaluated longitudinally every 2 weeks in 72 fetuses with severe isolated congenital diaphragmatic hernia. Thirty-five fetuses underwent fetal endoscopic tracheal occlusion and 37 cases did not. RESULTS: Survival rate was significantly higher in the fetal endoscopic tracheal occlusion group (54.3%) than in the no fetal endoscopic tracheal occlusion group (5.4%, P<.01). Fetal endoscopic tracheal occlusion resulted in a significant improvement in fetal lung size and pulmonary vascularity when compared with fetuses that did not go to the fetal intervention (increase of the observed-to-expected lung-to-head ratio, observed-to-expected total lung volume, and contralateral pulmonary vascularization index 56.2% compared with 0.3%, 37.9% compared with 0.1%, and 98.6% compared with 0.0%, respectively; P<.01). Receiver operating characteristic curves indicated that the observed-to-expected total fetal lung volume was the single best predictor of neonatal survival before fetal endoscopic tracheal occlusion (cutoff 0.23, area under the curve [AUC] 0.88, relative risk 5.3, 95% confidence interval [CI] 1.4-19.7). However, the contralateral lung vascularization index at 4 weeks after fetal endoscopic tracheal occlusion was more accurate in the prediction of neonatal outcome (cutoff 24.0%, AUC 0.98, relative risk 9.9, 95% CI 1.5-66.9) with the combination of observed-to-expected lung volumes and contralateral lung vascularization index at 4 weeks being the best predictor of outcome (AUC 0.98, relative risk 16.6, 95% CI 2.5-112.3). CONCLUSION: Fetal endoscopic tracheal occlusion improves survival rate by increasing the lung size and pulmonary vascularity in fetuses with severe congenital diaphragmatic hernia. The pulmonary response after fetal endoscopic tracheal occlusion can be used to predict neonatal survival. (Obstet Gynecol 2012; 119: 93-101) DOI: 10.1097/AOG.0b013e31823d3aea

A randomized controlled trial of fetal endoscopic tracheal occlusion versus postnatal management of severe isolated congenital diaphragmatic hernia

Objective Severe pulmonary hypoplasia and pulmonary arterial hypertension are associated with reduced survival in congenital diaphragmatic hernia (CDH). We aimed to determine whether fetal endoscopic tracheal occlusion (FETO) improves survival in cases of severe isolated CDH. Methods Between May 2008 and July 2010, patients whose fetuses had severe isolated CDH (lung-to-head ratio < 1.0, liver herniation into the thoracic cavity and no other detectable anomalies) were assigned randomly to FETO or to no fetal intervention (controls). FETO was performed under maternal epidural anesthesia supplemented with fetal intramuscular anesthesia. Tracheal balloon placement was achieved with ultrasound guidance and fetoscopy between 26 and 30 weeks of gestation. All cases that underwent FETO were delivered by the EXIT procedure. Postnatal therapy was the same for both treated fetuses and controls. The primary outcome was survival to 6 months of age. Other maternal and neonatal outcomes were also evaluated. Results Twenty patients were enrolled randomly to FETO and 21 patients to standard postnatal management. The mean gestational age at randomization was similar in both groups (P = 0.83). Delivery occurred at 35.6 +/- 2.4 weeks in the FETO group and at 37.4 +/- 1.9 weeks in the controls (P < 0.01). In the intention-to-treat analysis, 10/20 (50.0%) infants in the FETO group survived, while 1/21 (4.8%) controls survived (relative risk (RR), 10.5 (95% CI, 1.5-74.7), P < 0.01). In the receivedtreatment analysis, 10/19 (52.6%) infants in the FETO group and 1/19 (5.3%) controls survived (RR, 10.0 (95% CI, 1.4-70.6) P < 0.01). Conclusion FETO improves neonatal survival in cases with isolated severe CDH. Copyright (C) 2011 ISUOG. Published by John Wiley & Sons, Ltd.

Head-to-Head Comparison of Three Vaccination Strategies Based on DNA and Raw Insect-Derived Recombinant Proteins against Leishmania

Parasitic diseases plague billions of people among the poorest, killing millions annually, and causing additional millions of disability-adjusted life years lost. Leishmaniases affect more than 12 million people, with over 350 million people at risk. There is an urgent need for efficacious and cheap vaccines and treatments against visceral leishmaniasis (VL), its most severe form. Several vaccination strategies have been proposed but to date no head-to-head comparison was undertaken to assess which is the best in a clinical model of the disease. We simultaneously assayed three vaccination strategies against VL in the hamster model, using KMPII, TRYP, LACK, and PAPLE22 vaccine candidate antigens. Four groups of hamsters were immunized using the following approaches: 1) raw extracts of baculovirus-infected Trichoplusia ni larvae expressing individually one of the four recombinant proteins (PROT); 2) naked pVAX1 plasmids carrying the four genes individually (DNA); 3) a heterologous prime-boost (HPB) strategy involving DNA followed by PROT (DNA-PROT); and 4) a Control including empty pVAX1 plasmid followed by raw extract of wild-type baculovirus-infected T. ni larvae. Hamsters were challenged with L. infantum promastigotes and maintained for 20 weeks. While PROT vaccine was not protective, DNA vaccination achieved protection in spleen. Only DNA-PROT vaccination induced significant NO production by macrophages, accompanied by a significant parasitological protection in spleen and blood. Thus, the DNA-PROT strategy elicits strong immune responses and high parasitological protection in the clinical model of VL, better than its corresponding naked DNA or protein versions. Furthermore, we show that naked DNA coupled with raw recombinant proteins produced in insect larvae biofactories -the cheapest way of producing DNA-PROT vaccines-is a practical and cost-effective way for potential "off the shelf" supplying vaccines at very low prices for the protection against leishmaniases, and possibly against other parasitic diseases affecting the poorest of the poor.

DNA repair gene excision repair cross complementing-group 1 (ERCC1) in head and neck squamous cell carcinoma: analysis of methylation and polymorphism (G19007A), protein expression and association with epidemiological and clinicopathological factors

Aims: To evaluate the associations of excision repair cross complementing-group 1 (ERCC1) (DNA repair protein) (G19007A) polymorphism, methylation and immunohistochemical expression with epidemiological and clinicopathological factors and with overall survival in head and neck squamous cell carcinoma (HNSCC) patients. Methods and results: The study group comprised 84 patients with HNSCC who underwent surgery and adjuvant radiotherapy without chemotherapy. Bivariate and multivariate analyses were used. The allele A genotype variant was observed in 79.8% of the samples, GG in 20.2%, GA in 28.6% and AA in 51.2%. Individuals aged more than 45 years had a higher prevalence of the allelic A variant and a high (83.3%) immunohistochemical expression of ERCC1 protein [odds ratio (OR) = 4.86, 95% confidence interval (CI): 1.2-19.7, P = 0.027], which was also high in patients with advanced stage (OR= 5.04, 95% CI: 1.07-23.7, P = 0.041). Methylated status was found in 51.2% of the samples, and was higher in patients who did not present distant metastasis (OR = 6.67, 95% CI: 1.40-33.33, P = 0.019) and in patients with advanced stage (OR = 5.04, 95% CI: 1.07-23.7, P = 0.041). At 2 and 5 years, overall survival was 55% and 36%, respectively (median = 30 months). Conclusion: Our findings may reflect a high rate of DNA repair due to frequent tissue injury during the lifetime of these individuals, and also more advanced disease presentation in this population with worse prognosis.