Espina de pescado alojada en la glándula tiroides / Fishbone lodged in the thyroid gland

Los cuerpos extraños alojados en la vía aéreodigestiva superior son un motivo de consulta frecuente para el otorrinolaringólogo. Uno de los más frecuentes son las espinas de pescado. En raras ocasiones, éstas migran hacia tejidos adyacentes y generan complicaciones importantes. Presentamos el caso de una paciente que tras la ingesta de pescado manifiesta sensación de cuerpo extraño faríngeo, odinofagia y dolor látero cervical derecho. Dada la ausencia de hallazgos a la exploración física y laringoscópica se realiza una tomografia computarizada cervical, visualizando un cuerpo extraño alojado en la glándula tiroidea. Se interviene mediante cervicotomía media, realizando la extracción de la espina sin complicaciones. El diagnóstico precoz y manejo adecuado es determinante para prevenir complicaciones en estos casos.

Foreign bodies in the aerodigestive tract are commonly confronted in otolaryngology practice. The most frequent are the fish bones. In rare cases they can move and cause numerous complications. We report the case of a patient that manifest the sensation of pharyngeal foreign body, after fish ingestion. She also referred odynophagia and right cervical pain. Physical and laryngoscopic examination were normal. A cervical CT was performed, where a foreign body lodged in the thyroid gland was visualized, median cervicotomy was done and the foreign body was extracted. Early diagnosis and adequate management are crucial to prevent complications in these cases.

Role of major resection in pulmonary metastasectomy for colorectal cancer in the Spanish prospective multicenter study (GECMP-CCR).

BACKGROUND: Patients with pulmonary metastases from colorectal cancer (CRC) may benefit from aggressive surgical therapy. The objective of this study was to determine the role of major anatomic resection for pulmonary metastasectomy to improve survival when compared with limited pulmonary resection. PATIENTS AND METHODS: Data of 522 patients (64.2% men, mean age 64.5 years) who underwent pulmonary resections with curative intent for CRC metastases over a 2-year period were reviewed. All patients were followed for a minimum of 3 years. Disease-specific survival (DSS) and disease-free survival (DFS) were assessed with the Kaplan-Meier method. Factors associated with DSS and DFS were analyzed using a Cox proportional hazards regression model. RESULTS: A total of 394 (75.6%) patients underwent wedge resection, 19 (3.6%) anatomic segmentectomy, 5 (0.9%) lesser resections not described, 100 (19.3%) lobectomy, and 4 (0.8%) pneumonectomy. Accordingly, 104 (19.9%) patients were treated with major anatomic resection and 418 (80.1%) with lesser resection. Operations were carried out with video-assisted thoracoscopic surgery (VATS) in 93 patients. The overall DSS and DFS were 55 and 28.3 months, respectively. Significant differences in DSS and DFS in favor of major resection versus lesser resection (DSS median not reached versus 52.2 months, P = 0.03; DFS median not reached versus 23.9 months, P < 0.001) were found. In the multivariate analysis, major resection appeared to be a protective factor in DSS [hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.41-0.96, P = 0.031] and DFS (HR 0.5, 95% CI 0.36-0.75, P < 0.001). The surgical approach (VATS versus open surgical resection) had no effect on outcome. CONCLUSION: Major anatomic resection with lymphadenectomy for pulmonary metastasectomy can be considered in selected CRC patient with sufficient functional reserve to improve the DSS and DFS. Further prospective randomized studies are needed to confirm the present results.

Comparison of two HIV testing strategies in primary care centres: indicator-condition-guided testing vs. testing of those with non-indicator conditions.

OBJECTIVES: The aim of the study was to compare prospectively indicator-condition (IC)-guided testing versus testing of those with non-indicator conditions (NICs) in four primary care centres (PCCs) in Barcelona, Spain. METHODS: From October 2009 to February 2011, patients aged from 18 to 65 years old who attended a PCC for a new herpes zoster infection, seborrhoeic eczema, mononucleosis syndrome or leucopenia/thrombopenia were included in the IC group, and one in every 10 randomly selected patients consulting for other reasons were included in the NIC group. A proportion of patients in each group were offered an HIV test; those who agreed to be tested were given a rapid finger-stick HIV test (€6 per test). Epidemiological and clinical data were collected and analysed. RESULTS: During the study period, 775 patients attended with one of the four selected ICs, while 66,043 patients presented with an NIC. HIV screening was offered to 89 patients with ICs (offer rate 11.5%), of whom 85 agreed to and completed testing (94.4 and 100% acceptance and completion rates, respectively). In the NIC group, an HIV test was offered to 344 persons (offer rate 5.2%), of whom 313 accepted (90.9%) and 304 completed (97.1%) testing. HIV tests were positive in four persons [prevalence 4.7%; 95% confidence interval (CI) 1.3-11.6%] in the IC group and in one person in the NIC group (prevalence 0.3%; 95% CI 0.01-1.82%; P < 0.009). If every eligible person had taken an HIV test, we would have spent €4650 in the IC group and €396,258 in the NIC group, and an estimated 36 (95% CI 25-49) and 198 persons (95% CI 171-227), respectively, would have been diagnosed with HIV infection. The estimated cost per new HIV diagnosis would have been €129 (95% CI €107-153) in the IC group and €2001 (95% CI €1913-2088) in the NIC group. CONCLUSIONS: Although the number of patients included in the study was small and the results should be treated with caution, IC-guided HIV testing, based on four selected ICs, in PCCs seems to be a more feasible and less expensive strategy to improve diagnosis of HIV infection in Spain than a nontargeted HIV testing strategy.

Osteosarcomas de la región de cabeza y cuello / Osteosarcoma of the head and neck area: analysis of 12 patients

Background: Less than 10 percent of osteosarcomas are located the head and neck region, mainly affecting the mandible and maxillary region. Aim: To analyze the therapeutic modality, types of reconstruction, surgical complications and survival of patients treated for osteosarcoma of the head and neck. Material and Methods: Review of medical records of 12 patients aged 17 to 34 years (6 women) treated for osteosarcoma of the head and neck between September 1998 and may 2009. Results: The localization of the tumor was maxillary in eight, mandibular three and ethmoidal in one patient. According to histologic grade, seven tumors were grade 1, four were grade 2 and one was grade 3. Adjuvant and neoadjuvant chemotherapy were administered to all and seven patients, respectively. The surgical treatment for maxillary tumors was maxillectomy. A reconstruction with rectum abdomini free flap was done in four patients and with dermoepidermic graft and an obturator prosthesis in three. In one patient, the defect was covered with a dental prosthesis. Treatment for mandibular tumors was mandibular excision. A reconstruction with peroneal free flap was performed in two patients and with an iliac crest graft in one. The ethmoidal tumor was resected and covered with local flaps. There were four complications. Two patients had a cutaneous fistula, one patient had a free flap partial atrophy and one patient had surgical site infection. Two patients who had positive margins died from local recurrence. Of the 10 patients with negative margins, seven are alive without recurrence, one died due to the disease, one has disseminated disease and one died from another cause. Conclusions: Our results in the treatment of head and neck osteosarcomas are consistent with published data.

Objetivos: Analizar la modalidad terapéutica, tipos de reconstrucción, complicaciones quirúrgicas y sobrevida de un grupo de pacientes tratados por esta patología. Métodos: Revisión de fichas clínicas de 12 pacientes portadores de osteosarcoma de cabeza y cuello entre septiembre de 1998 y mayo de 2009. Resultados: Edad promedio 30 años (17-34), 6 mujeres y 6 hombres. Localización fue 8 maxilar, 3 mandibular y 1 etmoidales. 7 tumores G1, 4 G2 y 1 G3. Siete pacientes recibieron quimioterapia neoadyuvante y todos adyuvante. El tratamiento de tumores maxilares fueron maxilectomías reconstruidas 4 con colgajo libre de recto abdominal, 3 con injerto dermoepidérmico más prótesis obturadora y una con prótesis dentaria. Se realizó mandibulectomía a los tumores mandibulares, 2 reconstruidos con colgajo libre de peroné y uno con injerto de cresta ilíaca. El tratamiento del tumor etmoidal fue resección craneofacial y se reparó con colgajos locales. Hubo 4 complicaciones; 2 fístulas cutáneas, una atrofia parcial de colgajo libre y una infección de herida operatoria. Dos pacientes tuvieron bordes comprometidos, quienes murieron por recidiva local. De los 10 pacientes con bordes libres, 7 se encuentran sin evidencia de recidiva, uno con enfermedad diseminada, uno fallecido por la enfermedad y uno fallecido por otra causa. Conclusiones: Nuestros resultados son consistentes con la literatura.

Contractura axilar por quemadura tratada con Integra® / Axillary burn contracture treated with Integra®

Introduction: Severe axillary burn is an unusual accident that frequently evolves to contracture generating important cosmetic and functional deficiencies. Contracture scars in this region are difficult to treat because of the anatomic characteristics of the area that has multiple power vectors. Functional restoration has to be one of the main goals in the management of burns in the axilla and flaps have shown high rate of morbidity. Integra® provides satisfactory elasticity and dermal resistance which results in positive functional results. Objective: Analyze the results of the use of Integra® in axillary burn contracture scars at a specialized Burns Center. Materials and Methods: There were 4 patients who underwent reconstructive surgery using Integra® for axillary burn contractures between January 2002 and March 2006. Follow-up was divided into perioperative and late. Early follow-up checked general post-operative evolution and late follow-up was focused on functionality and patient independence evaluated using Barthel's index of daily living activities. Results: There were 3 males and 1 female, average age 27 (18-41) with a minimum follow up of 9 months. There were no perioperative complications and good or very good range of motion results. Conclusions: Our results are similar to artificial skin substitutes used in other anatomical regions.

Las quemaduras axilares severas son un accidente infrecuente que evolucionan a la retracción generando deficiencias cosméticas y funcionales. Estas cicatrices son difíciles de tratar por las características anatómicas del área, donde la corrección de un vector de movimiento puede alterar otro. Objetivo: Mostrar nuestros resultados utilizando el sustituto cutáneo Integra® en el tratamiento de cicatrices retráctiles axilares por quemadura. Pacientes y Métodos: Se recolectaron antecedentes médicos y fotográficos de pacientes portadores de cicatrices retráctiles axilares por quemadura entre enero de 2002 y marzo de 2006 en el Hospital del Trabajador de Santiago. Se evaluó pre y postoperatoriamente a los pacientes en forma subjetiva por fisiatra y con el Test de Barthel. Resultados: Se incluyeron 4 pacientes en el estudio (3 mujeres y 1 hombre), edad media 27 años (18-41). Todas las quemaduras fueron producidas por fuego. Índice de Barthel preoperatorio fue de 87,5 (levemente dependiente para las actividades de la vida diaria) y rango de movimiento moderadamente afectado. En el postoperatorio los pacientes fueron catalogados como independientes según el Test de Barthel y el rango de movimiento fue descrito como bueno o muy bueno por el fisiatra. No hubo complicaciones peri operatorias, Integra® prendió adecuadamente en todos los casos. Los pacientes fueron seguidos en promedio 16 meses (9-22). Conclusiones: Los sustitutos dérmicos han sido usados para la corrección de cicatrices de quemaduras con buenos resultados, pero no hay reportes en la axila. El pequeño número de pacientes que presentamos tienen un excelente resultado funcional, lo que nos estimula a seguir trabajando en este rumbo.

Total hip replacement in Gaucher's disease: effects of enzyme replacement therapy.

Total hip replacement in patients with Gaucher's disease with symptomatic osteonecrosis of the femoral head is controversial because of the high early failure rates. We describe four patients who had an uncemented total hip replacement following enzyme replacement therapy for a median of two years and one month (1 to 9.8 years) prior to surgery, and who remained on treatment. At operation, the bone had a normal appearance and consistency. Histopathological examination showed that, compared with previous biopsies of untreated Gaucher's disease, the Gaucher cell infiltrate had decreased progressively with therapy, being replaced by normal adipose tissue. The surfaces of viable bone beyond the osteonecrotic areas showed osteoblasts, indicating remodelling. In one case acetabular revision was carried out after 11 years and eight months. The three remaining patients had a mean follow-up of six years and four months (3.3 to 12 years). We recommend initiating enzyme replacement therapy at least one to two years prior to total hip replacement to facilitate bone remodelling and to allow implantation of uncemented components in these young patients.

Tracheal chondrosarcoma--a rare complication in Maffucci syndrome.

Maffucci syndrome is a rare congenital non-hereditary disease characterised by subcutaneous haemangiomata and multiple enchondromata. We present a case of an intermediate grade myxoid chondrosarcoma of the tracheal cartilage in a 34-year-old man with a history of Maffucci syndrome. Chondrosarcoma of the trachea are extremely rare tumours. A review of the radiological literature reveals approximately 15 previously published cases. No case was found with a history of Maffucci syndrome.

Colgajo miocutáneo de gastrocnemius medial con isla triangular de piel y cierre en V-Y / Gastrocnemius muscle myocutaneous flap with a triangular skin isle and V-Y closure: report of five patients

A gastrocnemius muscle myocutaneous flap with a triangular skin isle and V-Y closure can be used to correct cutaneous defects with exposure of the proximal part of the tibia. The advantages of this technique are an excellent irrigation and the cutaneous closure using a flap in a zone that is exposed to multiple trauma. The presence of a arteriovenous perforating vessel previously located with color Doppler, ensures the vitality of the flap. We report five males patients aged 20 to 70 years, in whom this technique as used to correct traumatic defects of a mean diameter of 11 cm. All flaps remained viable.

Para corregir defectos cutáneos con exposición de fractura de tibia a nivel del tercio proximal, una buena alternativa es el colgajo miocutáneo de gastrocnemius medial con isla triangular de piel con cierre en V-Y. Las ventajas estriban en la excelente irrigación del colgajo, y en proporcionar un cierre cutáneo con colgajo, en una zona expuesta a múltiples traumatismos. El hecho de tener una perforante arterio venosa previamente ubicada con doppler color, asegura la vitalidad del colgajo. Se presenta la experiencia del Servicio de Cirugía Plástica del Hospital del Trabajador de Santiago consistente en 5 pacientes masculinos en los que se realiza un colgajo de perforante de gastrocnemius medial, con edad entre 20 y 70 años. La etiología del defecto fue traumática. El defecto a corregir fue en promedio de 11 cms de diámetro. Todos los colgajos fueron viables. Se destaca que este es un colgajo inédito, descrito por primera vez por el autor principal en el año 2006.

Antifungal activities and cytotoxicity studies of six new azasordarins.

GW 471552, GW 471558, GW 479821, GW 515716, GW 570009, and GW 587270 are members of a new family of sordarin derivatives called azasordarins. The in vitro activities of these compounds were evaluated against clinical isolates of yeasts, including Candida albicans, Candida non-albicans, and Cryptococcus neoformans strains. Activities against Pneumocystis carinii, Aspergillus spp., less common molds, and dermatophytes were also investigated. Azasordarin derivatives displayed significant activities against the most clinically important Candida species, with the exception of C. krusei. Against C. albicans, including fluconazole-resistant strains, MICs at which 90% of the isolates tested are inhibited (MIC(90)s) were 0.002 microg/ml with GW 479821, 0.015 microg/ml with GW 515716 and GW 587270, and 0.06 microg/ml with GW 471552, GW 471558, and GW 570009. The MIC(90)s of GW 471552, GW 471558, GW 479821, GW 515716, GW 570009, and GW 587270 were 0.12, 0.12, 0.03, 0.06, 0.12, and 0.06 microg/ml, respectively, against C. tropicalis and 4, 0.25, 0.06, 0.25, 0.5, and 0.5 microg/ml, respectively, against C. glabrata. In addition, some azasordarin derivatives (GW 479821, GW 515716, GW 570009, and GW 58720) were active against C. parapsilosis, with MIC(90)s of 2, 4, 4, and 1 microg/ml, respectively. The compounds were extremely potent against P. carinii, showing 50% inhibitory concentrations of 16 microg/ml). These azasordarin derivatives also showed significant activity against emerging fungal pathogens, which affect immunocompromised patients, such as Rhizopus arrhizus, Blastoschizomyces capitatus, and Geotrichum clavatum. Against these organisms, the MICs of GW 587270 ranged from 0.12 to 1 microg/ml, those of GW 479821 and GW 515716 ranged from 0.12 to 2 microg/ml, and those of GW 570009 ranged from 0.12 to 4 microg/ml. Against Fusarium oxysporum, Scedosporium apiospermum, Absidia corymbifera, Cunninghamella bertholletiae, and dermatophytes, GW 587270 was the most active compound, with MICs ranging from 4 to 16 microg/ml. Against Aspergillus spp., the MICs of the compounds tested were higher than 16 microg/ml. The in vitro selectivity of azasordarins was investigated by cytotoxicity studies performed with five cell lines and primary hepatocytes. Concentrations of compound required to achieve 50% inhibition of the parameter considered (Tox(50)s) of GW 570009, GW 587270, GW 479281, and GW 515716 in the cell lines ranged from 60 to 96, 49 to 62, 24 to 36, and 16 to 38 microg/ml, respectively. The cytotoxicity values of GW 471552 and GW 471558 were >100 microg/ml for all cell lines tested. Tox(50)s on hepatocytes were in the following order: GW 471558 > GW 471552 > GW 570009 > GW 587270 > GW 515716 > GW 479821, with values ranging from higher than 100 microg/ml to 23 microg/ml. The cytotoxicity results obtained with fully metabolizing rat hepatocytes were in total agreement with those obtained with cell lines. In summary, the in vitro activities against important pathogenic fungi and the selectivity demonstrated in mammalian cell lines justify additional studies to determine the clinical usefulness of azasordarins.

[Assessment of mediastinal tumor involvement (T factor) in lung cancer with transesophageal ultrasonography]. / Evaluación de la afectación mediastínica tumoral (factor T) en el cáncer de pulmón mediante ecografía transesofágica.

UNLABELLED: Transesophageal sonography was originally used to assess esophageal-gastric neoplasm. The technique may also be useful in the evaluation of pulmonary neoplasms for possible mediastinal involvement, with regard to both T and N factors. OBJECTIVE: To consider the validity of this minimally-invasive technique for assessing possible mediastinal involvement by direct tumoral invasion (T4) and to help obtain the most accurate staging of lung cancer. PATIENTS AND METHODS: Sixteen patients with confirmed histopathological diagnoses of pulmonary neoplasm were examined by transesophageal sonography in order to evaluate possible mediastinal involvement. They had previously been classified by computed tomography as T4 (12 patients) or possible T4 (4 patients). Mediastinal involvement was also assessed by mediastinotomy or thoracotomy in 15 of the 16 patients. RESULTS: Transesophageal sonography revealed mediastinal involvement in eight of the 16 patients; the rest had no such involvement. Surgical exploration of the mediastinum confirmed involvement in seven of those who had been so classified by sonography (with the remaining patient not having been assessed surgically). Among the eight patients who were considered free of mediastinal involvement, there was in fact none, although we found previously undetected infiltration of the posterior surface of the right pulmonary artery in one patient. Sensitivity was 87.5%, specificity 100% and accuracy 93.3%. CONCLUSION: Transesophageal ultrasound is a diagnostic tool that can provide additional information to complement other diagnostic strategies.

[Surgical treatment of lung cancer: comparative assessment of the staging systems of 1986 and 1997. Results in 500 consecutive patients]. / Tratamiento quirúrgico del cáncer de pulmón: evaluación comparativa de los sistemas de estadificación de 1986 y 1997. Resultados en 500 pacientes consecutivos.

OBJECTIVE: To evaluate the influence of different variables on survival in relation to the staging guidelines of 1986 and 1997. PATIENTS AND METHODS: Five hundred patients (473 men and 27 women) with non-small cell lung cancer were treated surgically from 1980 to 1997. Resections performed: 184 lobectomies, 16 bi-lobectomies, 244 pneumonectomies, 2 bronchoplastic lobectomies, and 54 segmentectomies. HISTOLOGY: 338 epidermoid, 86 adenocarcinoma, 40 giant cell, 36 mixed tumor. Differentiation: 216 N1, 91 N2, 193 N3. Stages according to 1986 guidelines were I: 246 (49.2%) (T1: 32, T2: 214); II: 27 (5.4%); IIIa: 197 (39.4%) (N0: 84; N1: 2; N2: 111); IIIb: 23 (4.6%) (N0: 12; N2: 11); and IV: 7 (1.4%) (N0: 4; N2: 3). Stages according to the 1997 guidelines were used for comparison of survival between patients with Ia and Ib tumors and with IIb and IIIa tumors. RESULTS: With follow-up periods ranging from 2 to 17 years, 141 patients (28%) were alive, 26 (5%) were lost to follow-up and 333 had died. Two patients (0.4%) died during surgery and 36 (7.2%) died during the postoperative period. Among the remaining 462 patients, 295 deaths were related to the following causes: metastasis in 130 cases (44%), recurrence in 81 cases (27%), functional causes in 17 (6%), independent causes in 54 (18%) and unknown causes in 13 (4%). Overall survival rates at 5 and 10 years were 36 and 26%, respectively; survival rates by histological type: epidermoid 36 and 26%, adenocarcinoma 35 and 26%; stage I, 51 and 41% (Ia, 81 and 75%; Ib, 44 and 33%); IIIa 24 and 15% (IIb of 1997: 27 and 17%; IIIa of 1997: 20 and 13%). Survival by N factor: N0, 44 and 34%; N2, 17 and 8% (1986) and 17 and 11% (1997). CONCLUSIONS: Survival agrees with other studies. The 1997 staging guidelines are useful for differentiating survival between stages Ia and Ib and between IIb and IIIa. N and T factors, histology and stage influence the appearance of metastasis; T factor influences recurrence.

Prognostic factors in neuroendocrine lung tumors: a Spanish Multicenter Study. Spanish Multicenter Study of Neuroendocrine Tumors of the Lung of the Spanish Society of Pneumonology and Thoracic Surgery (EMETNE-SEPAR).

BACKGROUND: This study examines the experience of the Spanish Multicenter Study of Neuroendocrine Tumors of the Lung through the clinical data and behavior of patients treated for this pathologic process. METHODS: From 1980 to 1997, 361 cases of neuroendocrine carcinomas (NEC) were treated surgically. Patients were enrolled in a protocol using the pathologic and follow-up reports. According to Dreslers' criteria, the cases were segregated into grade 1 (typical carcinoid), grade 2 (atypical carcinoid), grade 3 large cell type, and grade 3 small cell type. Several variables were reviewed in all patients. Statistical analysis was performed to determine whether clinical characteristics and differentiation were associated with significant differences in the prognosis. RESULTS: A total of 261 cases of NEC were identified with grade 1, 43 with grade 2, and with grade 3: 22 of large and 35 of small cells. Five-year survival for different grades was as follows: grade 1, 96%; 2, 72%; 3 large cell type, 21%; and 3 small cell type, 14%. When a comparative analysis between typical and atypical carcinoids was performed a significant difference for mean age, tumor size, nodal metastases, and recurrence was observed. However, female sex, nodal metastases, and recurrence rate differed between atypical carcinoids and grade 3 NEC of large cells. A difference in recurrence rate was found between patients with both types of grade 3 NEC. CONCLUSIONS: The progressive deterioration of tumor organization highlights that neuroendocrine tumors constitute a continuous spectrum. A careful observation of pathologic findings is necessary to individualize their prognostic factors.

[Mediastinal hydatid cysts: 8 cases]. / Quistes hidatídicos de mediastino: 8 casos.

Hydatidosis in humans is a parasitic disease produced by cystic growth of the larvae of the tapeworm Echinococcus granulosus, affecting mainly the liver and lung. Larvae are rarely present in the mediastinum, although approximately 100 cases have been described in the literature. We report eight cases of hydatid cysts of the mediastinum (HCM) treated surgically over a period of 21 years. The incidence was similar in males and females and ages ranged from 10 to 74 years. Symptoms depend on size, location and involvement of neighboring structures in HCM. The most serious complication is cyst rupture with consequent transfer of hydatid material to the blood, possibly causing anaphylactic shock and even death. Currently, sonography, computed tomography and magnetic resonance images facilitate diagnosis. Treatment involves excision of the cyst and peri-cystic tissue. CHM should be suspected when mediastinal cysts are found in countries where the incidence of hydatidosis is high.

[Hemoptysis in a patient with a previous surgical correction of a tetralogy of Fallot]. / Hemoptisis en un paciente con el antecedente de corrección quirúrgica de una tetralogía de Fallot.

Aorto-bronchial fistula is a rare but associated with a height rare of mortality. Although most reported cases are secondary to infectious aneurysms, cases arising after surgery to correct congenital cardiovascular abnormalities have recently been described. We report the case of a 41-year-old patient with recurrent hemoptysis and a history of Fallot's tetralogy corrected in childhood. Given such a case of hemoptysis in a patient with a history of cardiovascular surgery, the correct diagnostic approach includes fiberoptic bronchoscopy, helicoidal CAT and/or NMR, and aortography. Diagnostic confirmation should be followed soon by corrective surgery.

Sordarins: in vitro activities of new antifungal derivatives against pathogenic yeasts, Pneumocystis carinii, and filamentous fungi.

GM 193663, GM 211676, GM 222712, and GM 237354 are new semisynthetic derivatives of the sordarin class. The in vitro antifungal activities of GM 193663, GM 211676, GM 222712, and GM 237354 against 111 clinical yeast isolates of Candida albicans, Candida kefyr, Candida glabrata, Candida parapsilosis, Candida krusei, and Cryptococcus neoformans were compared. The in vitro activities of some of these compounds against Pneumocystis carinii, 20 isolates each of Aspergillus fumigatus and Aspergillus flavus, and 30 isolates of emerging less-common mold pathogens and dermatophytes were also compared. The MICs of GM 193663, GM 211676, GM 222712, and GM 237354 at which 90% of the isolates were inhibited (MIC90s) were 0.03, 0.03, 0.004, and 0.015 microg/ml, respectively, for C. albicans, including strains with decreased susceptibility to fluconazole; 0.5, 0.5, 0.06, and 0.12 microg/ml, respectively, for C. tropicalis; and 0.004, 0.015, 0.008, and 0.03 microg/ml, respectively, for C. kefyr. GM 222712 and GM 237354 were the most active compounds against C. glabrata, C. parapsilosis, and Cryptococcus neoformans. Against C. glabrata and C. parapsilosis, the MIC90s of GM 222712 and GM 237354 were 0.5 and 4 microg/ml and 1 and 16 microg/ml, respectively. The MIC90s of GM 222712 and GM 237354 against Cryptococcus neoformans were 0.5 and 0.25 microg/ml, respectively. GM 193663, GM 211676, GM 222712, and GM 237354 were extremely active against P. carinii. The efficacies of sordarin derivatives against this organism were determined by measuring the inhibition of the uptake and incorporation of radiolabelled methionine into newly synthesized proteins. All compounds tested showed 50% inhibitory concentrations of <0.008 microg/ml. Against A. flavus and A. fumigatus, the MIC90s of GM 222712 and GM 237354 were 1 and 32 microg/ml and 32 and >64 microg/ml, respectively. In addition, GM 237354 was tested against the most important emerging fungal pathogens which affect immunocompromised patients. Cladosporium carrioni, Pseudallescheria boydii, and the yeast-like fungi Blastoschizomyces capitatus and Geotrichum clavatum were the most susceptible of the fungi to GM 237354, with MICs ranging from /=2 microg/ml. In summary, we concluded that some sordarin derivatives, such as GM 222712 and GM 237354, showed excellent in vitro activities against a wide range of pathogenic fungi, including Candida spp., Cryptococcus neoformans, P. carinii, and some filamentous fungi and emerging invasive fungal pathogens.