Tumor-like presentation of herpetic cervicitis: A case report.

The case of a 20-year-old immunocompetent woman with necrotizing cervicitis of the cervix caused by a primary infection with herpes simplex virus type 2 is presented, along with its respective evolution in images. Cervical cancer was included in the differential diagnoses, but biopsies ruled out malignancy and laboratory tests demonstrated the viral etiology of the cervical inflammation. After initiating specific treatment, the cervical lesions completely healed within 3 weeks. This case highlights the need to consider herpes simplex infection in the differential diagnosis of cervical inflammation and tumor formation. Additionally, it provides images that can aid in diagnosis and allow for the observation of its clinical evolution.

Hyperextension-distraction fractures in ankylosing and spondylotic spines: injury profile and treatment results.

STUDY DESIGN: Case series study. PURPOSE: To describe demographic metrics, and clinical and radiographical outcomes of surgical treatment in patients with ankylosed spine (ASP) such as diffuse idiopathic skeletal hyperostosis (DISH) or ankylosing spondylitis (AS) and non-ankylosed spines (NAS) suffering from hyperextension-distraction spine fractures. METHODS: Patients diagnosed with hyperextension-distraction fractures between 2012 and 2020 were identified. A retrospective analysis of clinical and surgical data was performed. Similarities between patients with ASP and NAS were evaluated by Fisher's exact test. RESULTS: Of the 22 patients, 13 had ASP (10 patients with DISH, 3 AS) and nine NAS. Most of these injuries involved the thoracolumbar spine (45.4%). All patients with NAS presented some sign of spondylosis: facet joint degeneration, intervertebral osteochondrosis, and anterolateral osteophytes. None of the patients with NAS and 30.7% with ASP suffered low-energy mechanisms (p = .11). All the patients with NAS and 61% of the patients with ASP had associated injuries (p = .04). On average, the instrumented levels were four (range, 2-6), achieving a fusion rate of 94.7% in all groups. Most of the ASP and NAS presented post-operative complications respectively (p = .65). CONCLUSION: Hyperextension-distraction spine fractures are not unique in ASP. In patients with spondylosis and high-energy accidents, we should suspect those fractures and rule out associated injuries, fractures in other vertebral segments, and acute spinal cord injury. The four-level instrumentation achieved an effective fusion rate in all patients.

Role of circulating tumor cells as prognostic marker in resected stage III colorectal cancer.

BACKGROUND: The prognostic role of circulating tumor cells (CTC) in early colorectal cancer (CRC) has not been determined yet. We evaluated the potential prognostic value of CTC in stage III CRC patients. PATIENTS AND METHODS: Prospective multicenter study of 519 patients with stage III CRC recruited between January 2009 and June 2010. CTC were enumerated with the CellSearch System after primary tumor resection and before the start of adjuvant therapy. A total of 472 patients were included in the analysis. RESULTS: CTC ≥1, ≥2, ≥3 and ≥5 were detected in 166 (35%), 93 (20%), 57 (12%) and 34 (7%) patients, respectively. Median follow-up was 40 months. In the overall population, CTC ≥1 (disease-free survival (DFS): HR 0.97, P = 0.85; overall survival (OS): HR 1.03, P = 0.89), ≥2 (DFS: HR 1.07, P = 0.76; OS: HR 1.02, P = 0.95), ≥3 (DFS: HR 0.96, P = 0.87; OS: HR 0.74, P = 0.41) and ≥5 (DFS: HR 0.72, P = 0.39; OS: HR 0.48, P = 0.21) were not associated with worse DFS and OS. No clinicopathological characteristics were significantly associated with the presence of CTC. In patients with disease relapse, the proportion with CTC ≥1 was not significantly different between those with single versus multiple metastatic locations (37.9% versus 31.4%, P = 0.761). In the multivariate analysis, CTC ≥1 was not an independent prognostic factor for DFS (HR 0.97, P = 0.87) and OS (HR 0.96, P = 0.89). CONCLUSION: CTC detection was not associated with worse DFS and OS in patients with stage III CRC. Given the scarcity of CTC in these patients, it is likely that CTC determined by CellSearch system does not have a prognostic role in this setting. However, a longer follow-up is needed.

Nuevas estrategias en el tratamiento del trauma raquimedular: actualización bibliográfica / New strategies in treatment of spinal cord injury: literature update

Better understanding of spinal cord injury pathophysiology has allowed the development of new areas of investigation, focused in reducing the injury and stimulating cord regeneration. The preliminary results of these investigations have generated great expectation in the scientific world, together with ambiguous information for patients with these injuries. In this article, we present a review of the available literature in this area, describing several non-pharmacological interventions, together with new drugs, immune therapies to block processes that inhibit cord regeneration and the renowned cell therapy. After evaluating the available articles included in this review, we observed a progress towards an increased efficacy of these treatments, but with limitations due to methodological flaws in the study protocols, which do not allow us to make applicability recommendations of them in humans.

Los recientes avances en el entendimiento de la fisiopatología del traumatismo raquimedular, han permitido el desarrollo de investigación enfocada en intervenciones orientadas a disminuir la lesión y estimular la regeneración medular. El entusiasmo por este nuevo conocimiento ha generado expectativa en el mundo científico co e información ambigua en los pacientes con este tipo de lesiones. En este trabajo revisamos la literatura reciente y la que se está llevando a cabo a este respecto, encontrando la descripción de algunas intervenciones no farmacológicas diferentes a la cirugía, nuevos medicamentos, terapias de bloqueo inmunológico de procesos que inhiben la regeneración medular y la reconocida terapia celular. Al evaluar los trabajos incluidos en esta revisión, observamos un avance hacia el aumento de la efectividad de los tratamientos pero con la limitación debida a las falencias metodológicas en la investigación que impiden hacer recomendaciones de aplicabilidad de los mismos en humanos.

[Haemophilia in the German risk adjustment scheme]. / Die Hämophilie im morbiditätsorientierten Risikostrukturausgleich.

Haemophilia presents a challenge to every risk adjustment scheme even if it uses diagnostical or pharmaceutical data. The German adjustment scheme developed by the Bundesversicherungsamt realizes fairly cost homogenous groups for many expensive diseases. It does not regard haemophilia. This holds true for the original classification system (grouper) from 2009 and for the improved classification procedure in 2010. The extreme peak costs that can originate from haemophilia cases can present a existential risk for small health plans. The chances to form cost-homogeneous subgroups of the haemophilia disease by more specific coding or other measures seem low because of the small number of cases affected by this disease. The complementary (re-)installation of a expenditure-oriented risk sharing is regarded as suited for improvement of the performance of the German risk adjustment scheme. This also corresponds to international experience and practice.

[Magnetic resonance imaging and magnetic resonance spectroscopy methods for measuring intra- and extra-cellular pH: clinical implications]. / Espectroscopía e imagen del pH intra y extracelular mediante métodos de resonancia magnética. Implicaciones clínicas.

We review the different methods for measuring pH by magnetic resonance imaging and magnetic resonance spectroscopy and discuss their potential diagnostic repercussions. We begin with a brief description of intra- and extra-cellular pH regulation in physiological and pathological conditions. Then we present the main 31P or 1H magnetic resonance spectroscopy procedures, which are based on the dependence of the pH on the chemical displacements of the intrinsic intracellular inorganic phosphate or of the H2 proton of imidazole in extrinsic indicators. Finally, we describe the procedures that use magnetic resonance imaging, whose main tool is the dependence of the pH (i) on the relaxivity of certain paramagnetic contrast agents, or (ii) on the processes of magnetic transference between diamagnetic molecules (DIACEST) or paramagnetic molecules (PARACEST) and the free water in the tissues. We briefly illustrate the potential clinical applications of these new procedures.

Espectroscopía e imagen del pH intra y extracelular mediante métodos de resonancia magnética. Implicaciones clínicas / Magnetic resonance imaging and magnetic resonance spectroscopy methods for measuring intraand extra-cellular pH: clinical implications

Se revisan los diversos métodos de medida de pH que utilizan espectroscopía e imagen por resonancia magnética y su potencial repercusión diagnóstica. La revisión comienza con una breve descripción de la regulación del pH intra y extracelular en condiciones fisiológicas y patológicas. Posteriormente se presentan los principales procedimientos basados en espectroscopía de resonancia magnética de 31P ó 1H, basados en la dependencia del pH de los desplazamientos químicos del fosfato inorgánico intracelular intrínseco o del protón H2 del imidazol en indicadores extrínsecos. Finalmente se describen los procedimientos que utilizan imagen por resonancia magnética, empleando como herramienta principal la dependencia del pH de (i) la relajatividad de determinados agentes de contraste paramagnéticos o (ii) de los procesos de transferencia de magnetización entre moléculas diamagnéticas (DIACEST) o paramagnéticas (PARACEST) y el agua libre de los tejidos. Se ilustran brevemente las potenciales aplicaciones clínicas de estos nuevos procedimientos

We review the different methods for measuring pH bymagnetic resonance imaging and magnetic resonance spectroscopy and discuss their potential diagnostic repercussions. We begin with a brief description of intra- and extracellular pH regulation in physiological and pathological conditions. Then we present the main 31P or 1H magnetic resonance spectroscopy procedures, which are based on the dependence of the pH on the chemical displacements of the intrinsic intracellular inorganic phosphate or of the H2 proton of imidazole in extrinsic indicators. Finally, we describe theprocedures that use magnetic resonance imaging, whosemain tool is the dependence of the pH (i) on the relaxivity of certain paramagnetic contrast agents, or (ii) on the processes of magnetic transference between diamagnetic molecules (DIACEST) or paramagnetic molecules (PARACEST) and the free water in the tissues. We briefly illustrate the potential clinical applications of these new procedures

[pulmonary thromboembolism in hospitalized patients during the period 1994-2000: an autopsy study]. / Tromboembolismo pulmonar en pacientes hospitalizados entre 1994-2000: serie de autopsia.

BACKGROUND: Pulmonary thromboembolism (PTE) has been for a long time a significant cause of morbidity and mortality in hospitalized patients. The utility of Low-Molecular Weight Heparins (LMWH) in these patients in the last decade of the XX century has decreased the incidence of this disease. We try to know if the massive useful of LMWH as thromboprophylasis is diminishing its incidence in autopsies. MATERIAL AND METHODS: Retrospective study of all the autopsies in adults in the Hospital Clínico San Carlos (Madrid) in a period of 6 years (from January 1994 to December 1999). There were reviewed those necropsies which had pathological data of pulmonary thromboembolism and several items were studied: anatomopathological, epidemiological, clinical and therapeutical. RESULTS: 483 necropsies were performed in this period; 40 (8.3%) had PE. Most of them were older than 50 years (85%) and the most important risk factors associated were bedridden, chronic cardiovascular diseases and malignant neoplasias. Only Pre-mortem diagnosis was only suspected in 5 patients (12.5%) and 15 of them (37.5%) had a fatal pulmonary embolism despite receipt of thromboprophylasis with LMWH. CONCLUSIONS: PTE is still an important cause of mortality in hospitalized patients. The increased of life expect, survival of chronic cardiovascular and malignant disease made PTE a frequent possibility situation in hospitalized patients. Receipt of LMWH as thromboprophylaxis is not always effective to avoid PTE.

Tromboembolismo pulmonar en pacientes hospitalizados entre 1994-2000: serie de autopsia / Pulmonary thromboembolism in hospitalized patients during the period 1994-2000: an autopsy study

Introducción: El tromboembolismo pulmonar (TEP) ha sido durante muchos años una causa muy importante de morbi-mortalidad en los pacientes hospitalizados. El empleo de forma profiláctica de Heparinas de Bajo Peso Molecular (HBPM) en pacientes ingresados en la última década del siglo XX parece haber disminuido de forma significativa su incidencia clínica. Pretendemos ver si el empleo de HBPM como medida de tromboprofilaxis ha modificado el hallazgo de esta patología en autopsias. Material y métodos: Estudio retrospectivo de todas las autopsias realizadas en adultos en el Hospital Clínico San Carlos (Madrid) en un periodo de 6 años (Enero 1994-Diciembre 1999). Se incluyeron en el estudio todas aquellas que presentaron hallazgos anatomopatológicos (AP) de TEP y se rellenó un protocolo en el que se incluyeron datos AP, datos epidemiológicos, clínicos y terapéuticos. Resultados: En el periodo estudiado se realizaron 483 necropsias, de las cuales 40 (8,3%) tenían datos de TEP. La mayor parte de ellos tenían más de 50 años (85%) y entre los factores de riesgo destacaron el reposo-encamamiento, la enfermedad crónica médica y la presencia de tumores malignos (adenocarcinomas). Sólo se sospechó el diagnóstico pre-mortem en 5 (12,5 %) y 15 (37,5 %) desarrollaron la ETE a pesar de haber recibido tratamiento profiláctico con HBPM. Conclusiones: El TEP continúa siendo una causa muy importante de mortalidad de los pacientes ingresados en el hospital. El aumento de la esperanza de vida, de la supervivencia de enfermedades crónicas médicas y tumorales determina que hay que tener muy en cuenta esta patología. El empleo de una HBPM como profilaxis no excluye la posibilidad de esta entidad

Background: Pulmonary thromboembolism (PTE) has been for a long time a significant cause of morbidity and mortality in hospitalized patients. The utility of Low-Molecular Weight Heparins (LMWH) in these patients in the last decade of the XX century has decreased the incidence of this disease. We try to know if the massive useful of LMWH as thromboprophylasis is diminishing its incidence in autopsies. Material y methods: Retrospective study of all the autopsies in adults in the Hospital Clínico San Carlos (Madrid) in a period of 6 years (from January 1994 to December 1999). There were reviewed those necropsies which had pathological data of pulmonary thromboembolism and several items were studied: anatomopathological, epidemiological, clinical and therapeutical. Results: 483 necropsies were performed in this period; 40 (8.3%) had PE. Most of them were older than 50 years (85%) and the most important risk factors associated were bedridden, chronic cardiovascular diseases and malignant neoplasias. Only Pre-mortem diagnosis was only suspected in 5 patients (12.5%) and 15 of them (37.5%) had a fatal pulmonary embolism despite receipt of thromboprophylasis with LMWH. Conclusions: PTE is still an important cause of mortality in hospitalized patients. The increased of life expect, survival of chronic cardiovascular and malignant disease made PTE a frequent possibility situation in hospitalized patients. Receipt of LMWH as thromboprophylaxis is not always effective to avoid PTE

Tumor de colisión renal: un caso inusual de carcinoma de células renales y leiomiosarcoma renal / Kidney collition tumor: an unusual case of renal cell carcinoma and renal leiomyosarcoma

Propósito: En el tumor de colisión coexistendos tumores histológicamente diferentes sin mezclaen la interfase. Los tumores de colisión que afectanal riñón son extremadamente raros.Material y métodos: Presentamos el caso deuna paciente con un tumor de colisión renal formadopor un carcinoma de células renales y un leiomiosarcomarenal.Resultados: El manejo clínico de este caso fuecomplejo debido a la escasa experiencia en el tratamientode este tipo de tumores y los pobres resultadosque se obtienen con el tratamiento sistémico enambos tipos de tumores.Conclusiones: Existen muy pocas comunicacionessobre tumores de colisión renales. Consideramosde interés el conocimiento sobre la existenciade estos tumores así como su complejidad clínica

Purpose: A collition tumor is characterized bythe coexistence of two histologically differentneoplasms that are independent of any interfacemixing. Kidney collition tumors are extremely rare.Material and methods: We present the caseof a patient diagnosed of a kidney collition tumorconsisting of renal cell carcinoma and renalleiomyosarcoma.Results: The clinical management of thispatient was complex due to the limited experiencein the treatment of his kind of tumors, and to thepoor results obtained with systemic treatment of thetwo types of tumors involved.Conclusions: There are very few communicationsabout collition tumors of the kidney, andwe consider interesting to repot the existence ofthese tumors as well as their clinical complexity

El acoso psicológico: riesgo laboral más frecuente de lo reportado / Psychological harassment: a more frequent labor risk than reported

Objetivo: revisar el acoso psicológico como una forma de violencia laboral a la cual está expuesta la población trabajadora en Colombia y en el mundo. Materiales y métodos: revisión narrativa del acoso psicológico en el trabajo, con énfasis en la situación actual colombiana. Resultados: el acoso psicológico en el trabajo se ha definido como un comportamiento irracional repetido con respecto a una persona o grupo de personas; crece y se desarrolla en el entorno laboral, afectando la salud psicológica, física y social de quien lo padece, de su familia y de quien lo ejecuta, así como el funcionamiento de las empresas. En Colombia, la prevalencia del acoso psicológico se ha reportado en un 19,8 por ciento; de agresión verbal en 12,8 por ciento; el jefe es el agresor más frecuente, con el 40 por ciento. Discusión: el evento estudiado es un fenómeno reciente aunque no novedoso, cuya tendencia mundial es creciente; en Colombia, los estudios realizados reportan proporciones superiores con relación a otros países y no existe legislación que lo controle. Conclusiones: el acoso psicológico en el trabajo es un riesgo laboral que debe prevenirse desde la salud pública para mitigar los daños causados a trabajadores, familia, empresa y sociedad.

Revisión y actualización de los protocolos de enfermería en una unidad de cirugía mayor ambulatoria / No disponible

No disponible

Phase II study of weekly irinotecan (CPT-11) as second-line treatment of patients with advanced colorectal cancer.

This phase II trial studied the antitumor effect and toxicity of weekly irinotecan (CPT-11, 125 mg/m(2) 60 min iv infusion, weekly for 4 wk plus 2 wk rest) as second-line chemotherapy in patients with advanced colorectal cancer (CRC) resistant or refractory to prior 5-fluorouracil (5-FU) therapy. Sixty-nine patients with adenocarcinoma (57% in the colon and 43% in the rectum) were enrolled. The median number of treatment cycles received per patient was 4 (range, 1-6). Overall response rate was 18% (95% CI, 9-26), with 4 complete responses (6%) and 8 partial responses (12%), and a median duration of response of 8.1 mo (95% CI, 4.2-12.1). Stable disease was observed in 19 patients (28%). The median time to disease progression was 5.2 mo (95% CI, 4.3-6.1), and the median overall survival was 13.3 mo (95% CI, 9.8-16.8 months). The toxicity profile was favorable: grade 3/4 delayed diarrhea was observed in 10 patients (14.5%) in one cycle each, and grade 3/4 neutropenia in 6 patients (8.7%) and 6 cycles (3.3%). No febrile neutropenia or infection was documented. Grade 3/4 nausea and vomiting were reported in 1 (1.4%) and 7 patients (10.1%), respectively. In conclusion, this phase II trial showed a response rate and a toxicity profile of weekly CPT-11 in line with the results of prior phase II studies.

Combined vascular and extracellular pH imaging of solid tumors.

The unique physiological environment of solid tumors, frequently characterized by areas of poor flow, hypoxia, high lactate and low extracellular pH (pHe), influences vascularization, invasion and metastasis. Thus, vascularization and the physiological and metabolic environment play permissive (and conversely preventive) roles in invasion and metastasis. By using a multi-parametric approach of combined vascular and spectroscopic imaging, we can begin to evaluate which combinations of vascular, metabolic and physiological regions in a solid tumor represent the highest 'metastatic threat'. Here, we present measurements of pHe, vascular volume and permeability from co-localized regions within a solid tumor. These studies were performed for a group of metastatic (MDA-MB-231) and non-metastatic (MCF-7) human breast cancer xenografts. In this study, we have demonstrated the feasibility of such an approach, and presented methods of analyses to detect differences in patterns of combined parameters obtained from spatially co-registered regions in a solid tumor.

Extraction and LC determination of lysine clonixinate salt in water/oil microemulsions.

A new reversed-phase high performance liquid chromatography method has been developed and validated for the quantitative determination of lysine clonixinate salt in water/oil microemulsions. The mobile phase was acetonitrile-buffer phosphate pH 3.3. Detection was UV absorbance at 252 nm. The precision and accurately of the method were excellent. The established linearity range was 5-60 microg ml(-1) (r(2)=0.999). Microemulsions samples were dispersed with chloroform and extracted lysine clonixinate salt with water. This easy method employing chloroformic extraction has been done three times. The recovery of lysine clonixinate salt from spiked placebo and microemulsion were >90% over the linear range.

Intracellular compartmentation of pyruvate in primary cultures of cortical neurons as detected by (13)C NMR spectroscopy with multiple (13)C labels.

The intracellular compartmentation of pyruvate in primary cultures of cortical neurons was investigated by high resolution (13)C NMR using mixtures of different pyruvate precursors conveniently labeled with (13)C or unlabeled. Cells were incubated with 1-5 mM (1-(13)C, 1,2-(13)C(2) or U-(13)C(6)) glucose only or with mixtures containing 1.5 mM (1-(13)C or U-(13)C(6)) glucose, 0.25-2.5 mM (2-(13)C or 3-(13)C) pyruvate and 1 mM malate. Extracts from cells and incubation media were analyzed by (13)C NMR to determine the relative contributions of the different precursors to the intracellular pyruvate pool. When ((13)C) glucose was used as the sole substrate fractional (13)C enrichments and (13)C isotopomer populations in lactate and glutamate carbons were compatible with a unique intracellular pool of pyruvate. When mixtures of ((13)C) glucose, ((13)C) pyruvate and malate were used, however, the fractional (13)C enrichments of the C2 and C3 carbons of lactate were higher than those of the C2 and C3 carbons of alanine and depicted a different (13)C isotopomer distribution. Moreover, neurons incubated with 1 mM (1,2-(13)C(2)) glucose and 0.25-5 mM (3-(13)C) pyruvate produced exclusively (3-(13)C) lactate, revealing that extracellular pyruvate is the unique precursor of lactate under these conditions. These results reveal the presence of two different pools of intracellular pyruvate; one derived from extracellular pyruvate, used mainly for lactate and alanine production and one derived from glucose used primarily for oxidation. A red-ox switch using the cytosolic NAD(+)/NADH ratio is proposed to modulate glycolytic flux, controlling which one of the two pyruvate pools is metabolized in the tricarboxylic acid cycle when substrates more oxidized or reduced than glucose are used.

Is obesity a contraindication to bilateral total knee arthroplasties under one anesthetic?

Three-hundred sixteen patients who underwent 405 primary knee replacements between January 1994 and June 1999 were reviewed for the incidence of local wound and systemic complications after unilateral and simultaneous bilateral total knee arthroplasties. A body mass index of 30 or greater was used to define obesity, and patients were divided into four groups based on obesity and whether they were undergoing unilateral or bilateral total knee arthroplasties. Preoperative and postoperative knee scores were not significantly different for any patient group. Local wound complication rates did not differ between any of the study groups. Patients who were not obese who underwent unilateral total knee arthroplasty had lower systemic complication rates (3%) than the other groups; however, there was no significant difference in complication rates between patients with obesity who underwent unilateral or simultaneous bilateral total knee arthroplasties. Based on these findings, obesity does not seem to be a contraindication to bilateral total knee arthroplasties under one anesthetic.

Mapping extracellular pH in rat brain gliomas in vivo by 1H magnetic resonance spectroscopic imaging: comparison with maps of metabolites.

The value of extracellular pH (pH(e)) in tumors is an important factor in prognosisand choice of therapy. We demonstrate here that pH(e) can be mappedin vivo in a rat brain glioma by (1)H magnetic resonance spectroscopic imaging (SI) of the pH buffer (+/-)2-imidazole-1-yl-3-ethoxycarbonylpropionic acid (IEPA). (1)H SI also allowed us to map metabolites, and, to better understand the determinants of pH(e), we compared maps of pH(e), metabolites, and the distribution of the contrast agent gadolinium1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraaceticacid (Gd-DOTA). C6 cells injected in caudate nuclei of four Wistar rats gave rise to gliomas of approximately 10 mm in diameter. Three mmols of IEPA were injected in the right jugular vein from t = 0 to t = 60 min. From t = 50 min to t = 90 min, spin-echo (1)H SI was performed with an echo time of 40 ms in a 2.5-mm slice including the glioma (nominal voxel size, 2.2 microl). IEPA resonances were detected only within the glioma and were intense enough for pH(e) to be calculated from the chemical shift of the H2 resonance in almost all voxels of the glioma. (1)H spectroscopic images with an echo time of 136 ms were then acquired to map metabolites: lactate, choline-containing compounds (tCho), phosphocreatine/creatine, and N-acetylaspartate. Finally, T(1)-weighted imaging after injection of a bolus of Gd-DOTA gave a map indicative of extravasation. On average, the gradient of pH(e) (measured where sufficient IEPA was present) from the center to the periphery was not statistically significant. Mean pH(e) was calculated for each of the four gliomas, and the average was 7.084 +/- 0.017 (+/- SE; n = 4 rats), which is acid with respect to pH(e) of normal tissue. After normalization of spectra to their water peak, voxel-by-voxel comparisons of peak areas showed that N-acetylaspartate, a marker of neurons, correlated negatively with IEPA (P < 0.0001) and lactate (P < 0.05), as expected of a glioma surrounded by normal tissue. tCho (which may indicate proliferation) correlated positively with pH(e) (P < 0.0001). Lactate correlated positively with tCho (P < 0.0001), phosphocreatine/creatine (P < 0.001), and Gd-DOTA (P < 0.0001). Although lactate is exported from cells in association with protons, within the gliomas, no evidence was observed that pH(e) was significantly lower where lactate concentration was higher. These results suggest that lactate is produced mainly in viable, well-perfused, tumoral tissue from which proton equivalents are rapidly cleared.

In vivo imaging of extracellular pH using 1H MRSI.

Tumor pH is physiologically important since it influences a number of processes relevant to tumorigenesis and therapy. Hence, knowledge of localized pH within tumors would contribute to understanding these processes. The destructiveness, poor spatial resolution, and poor signal-to-noise ratio (SNR) of current technologies (e.g., microelectrodes, 31P magnetic resonance spectroscopy) have limited such studies. An extrinsic chemical extracellular pH (pHe) probe is described that is used in combination with 1H magnetic resonance spectroscopic imaging to yield pHe maps with a spatial resolution of 1 x 1 x 4 mm3. The principle of the technique is demonstrated on a phantom. Further data are shown to demonstrate its application in vivo, and results agree with previously reported pH values. The accuracy of the reported pH measurements is <0.1 pH units, as derived from a detailed analysis of the errors associated with the technique, the description of which is included.

N-2-(azol-1(2)-yl)ethyliminodiacetic acids: a novel series of Gd(III) chelators as T2 relaxation agents for magnetic resonance imaging.

The synthesis, physicochemical properties, and toxicological implications of a novel series of N-2-(azol-1(2)-yl)ethyliminodiacetic acids, useful as contrast agents for magnetic resonance imaging are reported. Compounds were prepared by alkylation of methyl iminodiacetate with N-2-bromoethylazoles and subsequent hydrolysis. Stability constants of the corresponding Gd(III) complexes and T1 and T2 relaxivities were determined and interpreted in terms of optimized geometries obtained by semiempirical PM3 calculations. Compounds show increased T2 relaxivity and decreased toxicity in vitro as compared to EDTA-Gd(III) complexes.