Assessment of folate receptor-α and epidermal growth factor receptor expression in pemetrexed-treated non-small-cell lung cancer patients.

INTRODUCTION: Folate receptor-α regulates cellular uptake of folates and antifolates (eg, pemetrexed) and is frequently expressed in pulmonary adenocarcinoma. EGFR is an established therapeutic target in NSCLC. Therapies targeting FRA or EGFR are available. The association between FRA and EGFR expression in advanced NSCLC has not been explored. Combining therapeutic FRA antibodies with an EGFR inhibitor might be beneficial, if both of the targets are significantly coexpressed. PATIENTS AND METHODS: Specimens from 160 advanced NSCLC patients receiving pemetrexed-based chemotherapy were assessed for membranous FRA and EGFR protein expression using immunohistochemistry and the Hybrid (H)-score. EGFR (exons 18-21) and Kirsten RNA-associated rat sarcoma 2 virus (exon 2) mutations were determined. Results were correlated to patients' clinicopathological data, progression-free survival (PFS), and overall survival (OS). RESULTS: Forty-seven patients (29%) had tumors with strong FRA and EGFR expression, but no statistically significant correlation was seen between protein levels of FRA and EGFR. High membranous FRA expression (H-score ≥ 20) was associated with prolonged PFS (5.5 vs. 3.4 months; hazard ratio [HR], 0.6060; P = .0254) and improved OS (12.1 vs. 6.4 months; HR, 0.5726; P = .0076). CONCLUSION: Survival times are improved in NSCLC patients whose tumors show strong membranous FRA expression. No statistical correlation between membranous FRA and EGFR expression was demonstrated in advanced NSCLC, but 47 patients (29%) had higher expression of both of the receptors and could be suitable for combined targeted therapies.

Patent foramen ovale in trigeminal autonomic cephalalgias and hemicrania continua: a non-specific pathophysiological occurrence?

Patent foramen ovale (PFO), a relatively common abnormality in adults, has been associated with migraine. Few studies also linked PFO with cluster headache (CH). To verify whether right-to-left shunt (RLS) is related to headaches other than migraine and CH, we used transcranial Doppler following microbubbles injection to detect shunts in 24 CH, 7 paroxysmal hemicrania (PH), one SUNCT, two hemicrania continua (HC) patients; and 34 matched controls. RLS was significantly more frequent in CH than in controls (54% vs. 25%, p=0.03), particularly above the age of 50. In the HC+PH+SUNCT group, RLS was found in 6 patients and in 2 controls (p=0.08). Smoking as well as the Epworth Sleepiness Scale correlated significantly with CH, smoking being more frequent in patients with RLS. PFO may be non-specifically related to trigeminal autonomic cephalalgias and HC. The headache phenotype in PFO patients probably depends on individual susceptibility to circulating trigger factors.

Patent foramen ovale in trigeminal autonomic cephalalgias and hemicrania continua: a non-specific pathophysiological occurrence? / Foramen oval patente em cefaleias trigêmino-autonômicas e hemicrania contínua: uma ocorrência fisiopatológica não específica?

Patent foramen ovale (PFO), a relatively common abnormality in adults, has been associated with migraine. Few studies also linked PFO with cluster headache (CH). To verify whether right-to-left shunt (RLS) is related to headaches other than migraine and CH, we used transcranial Doppler following microbubbles injection to detect shunts in 24 CH, 7 paroxysmal hemicrania (PH), one SUNCT, two hemicrania continua (HC) patients; and 34 matched controls. RLS was significantly more frequent in CH than in controls (54 percent vs. 25 percent, p=0.03), particularly above the age of 50. In the HC+PH+SUNCT group, RLS was found in 6 patients and in 2 controls (p=0.08). Smoking as well as the Epworth Sleepiness Scale correlated significantly with CH, smoking being more frequent in patients with RLS. PFO may be non-specifically related to trigeminal autonomic cephalalgias and HC. The headache phenotype in PFO patients probably depends on individual susceptibility to circulating trigger factors.

O forame oval patente (FOP), uma anormalidade cardíaca relativamente comum em adultos, tem sido associado à enxaqueca, mas raramente às cefaléias trigêmino-autonômicas (TACs). Utilizamos o Doppler transcraniano (DTC) para detecção de shunt direito-esquerdo (SDE) em 24 pacientes com cefaléia em salvas (CS), sete com hemicrania paroxística (HP), dois com hemicrania continua (HC) e um com SUNCT; alem de 34 controles. O SDE foi mais frequente nos pacientes com CS do que nos controles (54 por cento vs. 25 por cento p=0,03), particularmente acima de 50 anos. No grupo HP+HC+SUNCT, o SDE foi encontrado em seis pacientes e dois controles (p=0,08). O hábito de fumar, bem como sonolência excessiva diurna foram mais frequentes em paciente com CS. O FOP pode ter importância inespecífica na fisiopatologia das TACs e HC, na dependência da susceptibilidade individual a fatores desencadeantes.

Transoral approach to the craniovertebral junction

The transoral approach provides a safe exposure to lesions in the midline and the ventral side of the craniovertebral junction. The advantages of the transoral approach are 1) the impinging bony pathology and granulation tissue are accessible only via the ventral route; 2) the head is placed in the extended position, thus decreasing the angulation of the brainstem during the surgery; and 3) surgery is done through the avascular median pharyngeal raphe and clivus. We analyzed the clinical effects of odontoidectomy after treating 38 patients with basilar invagination. The anterior transoral operation to treat irreducible ventral compression in patients with basilar invagination was performed in 38 patients. The patientsÆ ages ranged from 34 to 67 years. Fourteen patients had associated Chiari malformation and eight had previously undergone posterior decompressive surgery. The main indication for surgery was significant neurological deterioration. Symptoms and signs included neck pain, myelopathy, lower cranial nerve dysfunction, nystagmus and gait disturbance. Extended exposure was performed in 24 patients. The surgery was beneficial to the majority of patients. There was one death within 10 days of surgery, due to pulmonary embolism. Postoperative complications included two cases of pneumonia, three cases of oronasal fistula with regurgitation and one cerebrospinal fluid leak. In patients with marked ventral compression, the transoral approach provides direct access to the anterior face of the craniovertebral junction and effective means for odontoidectomy.

O acesso transoral é uma via direta e segura às lesões situadas na linha média e na face anterior da junção craniocervical. As vantagens do acesso transoral são as seguintes:1) a compressão óssea e o tecido de granulação localizam-se anteriormente e são accessíveis pela via anterior; 2) a cabeça do paciente é colocada em extensão, diminuindo a angulação do tronco cerebral durante a cirurgia; e 3) a cirurgia é feita através de um plano avascular na linha média faríngea e clivo. Analisamos os resultados obtidos após odontoidectomia por via transoral em 38 pacientes portadores de invaginação basilar. Trinta e oito pacientes com compressão ventral da junção craniocervical foram submetidos a odontoidectomia por via transoral. A idade dos pacientes variou de 34 a 67 anos. Quatorze pacientes apresentavam associação com malformação de Chiari tipo I e 8 já haviam sido submetidos à cirurgia descompressiva por via posterior. A maioria dos pacientes apresentou nucalgia, mielopatia, déficits dos nervos cranianos baixos, nistagmo, e distúrbio da marcha. Em 24 pacientes foi necessário ampliar o acesso transoral através de miotomia do palato mole, ou osteotomia do palato duro ou maxilotomia. A cirurgia proporcionou melhora dos sintomas na maioria dos pacientes. Um paciente faleceu no pós-operatório imediato por causa de embolia pulmonar. Dois pacientes tiveram pneumonia, três apresentaram fístula oronasal com regurgitação, e um teve fístula liquórica. Em pacientes com compressão ventral irredutível da junção craniocervical, a via transoral proporcionou uma abordagem direta e ampla ao processo odontoide.

Transoral approach to the craniovertebral junction.

The transoral approach provides a safe exposure to lesions in the midline and the ventral side of the craniovertebral junction. The advantages of the transoral approach are 1) the impinging bony pathology and granulation tissue are accessible only via the ventral route; 2) the head is placed in the extended position, thus decreasing the angulation of the brainstem during the surgery; and 3) surgery is done through the avascular median pharyngeal raphe and clivus. We analyzed the clinical effects of odontoidectomy after treating 38 patients with basilar invagination. The anterior transoral operation to treat irreducible ventral compression in patients with basilar invagination was performed in 38 patients. The patients ages ranged from 34 to 67 years. Fourteen patients had associated Chiari malformation and eight had previously undergone posterior decompressive surgery. The main indication for surgery was significant neurological deterioration. Symptoms and signs included neck pain, myelopathy, lower cranial nerve dysfunction, nystagmus and gait disturbance. Extended exposure was performed in 24 patients. The surgery was beneficial to the majority of patients. There was one death within 10 days of surgery, due to pulmonary embolism. Postoperative complications included two cases of pneumonia, three cases of oronasal fistula with regurgitation and one cerebrospinal fluid leak. In patients with marked ventral compression, the transoral approach provides direct access to the anterior face of the craniovertebral junction and effective means for odontoidectomy.

The history of spinal surgery for disc disease: an illustrated timeline.

This article presents the evolution in medical history which leads to the surgical treatment for ruptured discs. Only at the last century the precise diagnosis of a ruptured lumbar disc could be made after tremendous efforts of the many medical pioneers in the study of the spine. The experience gained with the lumbar spine was rapidly transferred to the cervical spine. We describe the evolution of the clinical and surgical aspects about ruptured discs in the lumbar and cervical spine. An illustrative timeline of the major events regarding the surgical treatment for ruptured disks is outlined in a straight forward manner. Our understandings of the relation between symptoms and signs and of that between anatomy and pathophysiology have led to more successful surgical treatment for this disease. Nowadays lumbar and cervical discectomies are the most frequent operations carried out by neurosurgeons. Our current care of patients with this kind of spinal disorders is based on the work of our ancient medical heroes.

The history of spinal surgery for disc disease: an illustrated timeline

Esse artigo apresenta a evolução da história médica que nos conduziu ao tratamento cirúrgico da doença discal. Somente no século passado o diagnóstico preciso de ruptura de disco lombar pode ser feito, após os esforços de vários pioneiros no estudo da coluna vertebral. A experiencia obtida no estudo da coluna lombar foi rapidamente transferida para coluna cervical. Uma revisão ilustrada dos principais eventos relacionados ao tratamento cirúrgico do disco roto na coluna lombar e cervical é apresentada de forma objetiva. Nosso conhecimento sobre a relação entre os sinais e sintomas, da anatomia e fisiopatologia levaram ao tratamento cirúrgico mais eficaz das lesões discais. O tratamento atual dessas anormalidades da coluna vertebral é fruto do trabalho de verdadeiros médicos e heróis.

Internal structure of the cerebral hemispheres: an introduction of fiber dissection technique.

The aim of this study is to introduce the fiber dissection technique and its importance in the comprehension of the three-dimensional intrinsic anatomy of the brain. A total of twenty brain hemispheres were dissected. Using Kingler's technique we demonstrated the intrinsic structures of the brain. The supra lateral aspect of the brain as well as the medial aspect were presented. The most important fiber systems were demonstrated. The use and comprehension of new neuroimaging techniques demand a better understanding of this fascinating anatomy. The knowledge acquired with this technique will improve our understanding of critical pathways of the central nervous system.

Internal structure of the cerebral hemispheres: an introduction of fiber dissection technique

O objetivo é mostrar a técnica de dissecação de fibras e sua importância na compreensão da anatomia tridimensional do cérebro. Um total de 20 hemisférios cerebrais foram dissecados. Usando a técnica de dissecação descrita por Kingler, pudemos demonstrar as estruturas que compõem a anatomia interna do cérebro. A anatomia da face súpero-lateral assim como da face medial foi apresentada. O uso e compreensão de novas técnicas de neuroimagem requerem um melhor conhecimento desta anatomia. O conhecimento adquirido com essa técnica contribuirá para o melhor entendimento de vias essenciais do sistema nervoso central.

Combined supra/infratentorial approach to tentorial meningiomas.

In spite of significant advancements in imaging technology, monitoring, and microsurgical techniques, complete and safe removal of tentorial meningiomas remains a challenge for most neurosurgeons. Classifications of tentorial meningiomas are revised. The combined supra/infratentorial approach to resect tentorial meningioma is discussed. This approach provides a wider exposure of the supra/infratentorial region with less brain retraction. With this approach the occipital lobe and the cerebellum are exposed along the tentorium. Two illustrative cases are presented. The patients were studied with computerized tomography, magnetic resonance and angiography. The anatomy of the transverse sinus and the confluence of the sinus could be appreciated with these studies. The operative technique is described stepwise. Emphasis is placed on pre-operative evaluation and surgical technique, leading to a total surgical removal of the lesion with margins of safety. The goal of surgical treatment of tentorial meningiomas is their complete and safe removal. With this unique approach we sought to confirm that it offers a safe means of resection not only the neoplasm but also the infiltrated dura.

Combined supra/infratentorial approach to tentorial meningiomas

Apesar dos significativos avanços na tecnologia de imagens, nas técnicas de monitorização e microcirúrgicas, a ressecção completa e segura dos meningiomas tentoriais permanece um desafio para maioria dos neurocirurgiões. A abordagem supra e infra-tentorial proporciona ampla exposição das regiões supra e infratentoriais diminuindo a retração cerebral. Com esse tipo de abordagem o lobo occiptal e o cerebelo são expostos ao longo da superficie tentorial. Dois casos ilustrativos são apresentados. Os pacientes foram avaliados com tomografia computadorizada, ressonância magnética e angiografia, o que permitiu estudar a anatomia do seio transverso, a confluência e dominancia dos seios. O objetivo do tratamento cirúrgico dos meningiomas tentoriais é a remoção completa e segura. A associação das imagens, o acesso combinado e a técnica microcirúrgica permitem a remoção cirúrgica total deste tipo de lesão e do implante dural com margens de segurança.

Aldosterone and high-NaCl diet modulate ClC-2 chloride channel gene expression in rat kidney.

It is well known that Na+ reabsorption in the kidney can be regulated by aldosterone. Although Cl- is the most abundant anion present in the extra cellular fluids the involvement of aldosterone in the regulation of Cl- conductance through Cl- channels at the molecular level is unknown. In this study, the effects of aldosterone and high-Na+ diet on the expression of ClC-2, a cell volume-, pH- and voltage-sensitive Cl- channel, was examined in the rat kidney. Total RNA isolated from Wistar rats fed a high-Na+ diet for 5 days, furosemide treatment, adrenalectomy and adrenalectomy with replacement of normal plasma levels of aldosterone were compared by the use of ribonuclease protection assay (RPA), and/or a semi-quantitative RT-PCR. The high-Na+ diet reduced renal mRNA and protein ClC-2 expression. The renal expression of ClC-2 mRNA decreased in adrenalectomized rats and was restored by plasma aldosterone replacement. In addition, the semi-quantitative RT-PCR in different segments of the nephron showed that these changes were secondary to the modulation of ClC-2 mRNA expression by aldosterone in the cortical and medullary segments of thick ascending limbs of Henle's loop. These results suggest that ClC-2 may be involved with aldosterone-induced Cl- transport in the kidney.