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1.
Clin Microbiol Infect ; 26(3): 351-357, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31288102

ABSTRACT

OBJECTIVES: We assessed the association between the lethality of Pseudomonas aeruginosa in a Caenorhabditis elegans model and outcomes of P. aeruginosa bloodstream infections. METHODS: A total of 593 P. aeruginosa bloodstream isolates recovered from a prospective Spanish multicentre study were analysed. Clinical variables, susceptibility profiles and Type III Secretion System (TTSS) genotypes (exoU/exoS genes) were available from previous studies. A C. elegans virulence score (CEVS) was used, classifying the isolates into high (CEVS 4-5), intermediate (CEVS 3) and low (CEVS 1-2) virulence. The main outcome analysed was 30-day mortality. RESULTS: Up to 75% (446/593) of the isolates showed a high-virulence phenotype, and 17% (101/593) a low-virulence one. No association between virulence phenotype and the main outcome variable (30-day mortality) was found (29/101 (28.7%) versus 127/446 (28.5%), p 1). However, an inverse association between C. elegans virulence and multidrug-resistant and extensively drug-resistant profiles was documented (OR 0.655 (95% CI 0.571-0.751) and OR 0.523 (95% CI 0.436-0.627), p <0.001, respectively), whereas the exoU genotype was significantly more frequent among isolates showing high virulence (10/101 (9.9%) versus 112/446 (25.1%), p <0.001). Moreover, although significance was not reached, strains showing a high-virulence phenotype tended to be associated with community-acquired infections (1/101 (1%) versus 25/446 (5.6%), p 0.065), whereas low-virulence phenotypes tended to be associated with a higher illness severity (such as higher median Pitt score: 2 (1-4) versus 1 (0-3), p 0.036, or initial multiorgan dysfunction: 17/101 (16.8%) versus 41/446 (9.2%), p 0.024), with some underlying conditions (such as chronic renal failure 24/101 (23.8%) versus 59/446 (13.2%), p 0.013), and with the respiratory source of infections (17/101 (16.8%) versus 45/446 (10.1%), p 0.058). CONCLUSIONS: Our results indicate that the P. aeruginosa virulence phenotype in a C. elegans model correlates with virulence genotype (TTSS) and resistance profile, but it is a poor prognostic marker of mortality in bloodstream infections.


Subject(s)
Bacteremia/epidemiology , Pseudomonas Infections/epidemiology , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/pathogenicity , Aged , Aged, 80 and over , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacterial Proteins/genetics , Bacterial Secretion Systems/genetics , Drug Resistance, Bacterial , Female , Genotype , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Patient Outcome Assessment , Phenotype , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa/classification , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/genetics , Public Health Surveillance , Virulence , Virulence Factors/genetics
2.
Prev Med ; 86: 147-52, 2016 May.
Article in English | MEDLINE | ID: mdl-26944518

ABSTRACT

OBJECTIVE: To compare the current breast cancer prevention and control Mexican standard with recommendations that health care professionals provide to women for breast self-exams, clinical breast exams and mammography, as well as health care professional knowledge of the risk factors for and main clinical signs of the disease. METHODS: In 2012, using a cross-sectional design, trained interviewers surveyed health care providers in a sample of 798 medical units, of which 756 corresponded to the first and second levels of medical care. One health care professional from each unit was interviewed for the study. The sampling method was systematic and representative of the national and regional levels. Relative frequencies and 95% confidence intervals (CI) were obtained using the weighting factor assigned to each medical unit. RESULTS: Regarding the indicator about recommendations provided to the population regarding early screening for and risk factors and clinical signs of breast cancer, the average number of health care professional responses in accordance with the Mexican standard was 10.7 (95% CI 10.0-11.4) out of a maximum of 28 points, which corresponds to an average rate of 38.2% of responses (95% CI 35.6-40.8). The percentage of correct answers increased in all areas of breast exam knowledge as training hours in the previous year increased. CONCLUSIONS: Health care professionals are unaware of the current standards on breast cancer; therefore, these recommendations are not routinely translated into health care practice, which is a barrier to increasing the coverage of screening programs in health care services.


Subject(s)
Breast Neoplasms/diagnosis , Early Detection of Cancer/statistics & numerical data , Health Knowledge, Attitudes, Practice , Health Personnel/statistics & numerical data , Adult , Aged , Cross-Sectional Studies , Female , Health Personnel/psychology , Humans , Interviews as Topic , Male , Mammography/psychology , Mammography/statistics & numerical data , Middle Aged , Morocco/epidemiology , Primary Health Care/statistics & numerical data , Risk Factors , Secondary Care/statistics & numerical data
3.
Eur J Clin Microbiol Infect Dis ; 35(2): 195-200, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26638216

ABSTRACT

Pseudomonas aeruginosa multidrug resistance, and particularly the production of carbapenemases linked to international high-risk clones, is of growing concern. While high levels of carbapenem resistance (>60 %) have been reported in Lithuania, so far, there is no information on the underlying mechanisms. Thus, the aim of this work was to determine the molecular epidemiology and prevalence of acquired carbapenemases among 73 carbapenem-resistant P. aeruginosa isolates recovered in a hospital from Kaunas, Lithuania in 2011-2012. The presence of acquired carbapenemases was evaluated through phenotypic (modified Hodge test, cloxacillin inhibition test, double-disc synergy test) and genetic methods [polymerase chain reaction (PCR) and sequencing]. Clonal relatedness was assessed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Acquired ß-lactamases were detected in 19 (26 %) of the isolates, whereas resistance was exclusively chromosomal (OprD inactivation ± AmpC hyperproduction) in the remaining 54 (74 %) isolates. The acquired ß-lactamases detected included 16 VIM-2, one PER-1 and two GES enzymes. PFGE revealed that 15 of the 16 VIM-2 isolates belonged to a single clone, identified as the international high-risk clone ST235 by MLST. bla VIM-2 was preceded by aacA7 in a class I integron, similar to epidemic ST235 isolates described in nearby countries. Additionally, sequencing of bla GES revealed the presence of the carbapenem-hydrolysing enzyme GES-5 in one of the isolates and a novel GES variant, designated GES-27, in the other. GES-27 differed from GES-5 by a single amino acid substitution, proline 167, that was replaced by glutamine. Increasing emergence and dissemination of concerning resistance mechanisms and international clones warrants global surveillance and control strategies.


Subject(s)
Bacterial Proteins/metabolism , Drug Resistance, Multiple, Bacterial/genetics , Pseudomonas Infections/drug therapy , Pseudomonas Infections/epidemiology , Pseudomonas aeruginosa/pathogenicity , beta-Lactamases/metabolism , Anti-Bacterial Agents/therapeutic use , Carbapenems/therapeutic use , Cross Infection/epidemiology , Cross Infection/microbiology , DNA, Bacterial/genetics , Electrophoresis, Gel, Pulsed-Field , Humans , Lithuania/epidemiology , Microbial Sensitivity Tests , Molecular Epidemiology , Multilocus Sequence Typing , Polymerase Chain Reaction , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/metabolism
4.
Antimicrob Agents Chemother ; 59(9): 5260-6, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26077249

ABSTRACT

We examined the genetic context of 74 acquired ampC genes and 17 carbapenemase genes from 85 of 640 Enterobacteriaceae isolates collected in 2009. Using S1 pulsed-field gel electrophoresis and Southern hybridization, 37 of 74 bla AmpC genes were located on large plasmids of different sizes belonging to six incompatibility groups. We used sequencing and PCR mapping to investigate the regions flanking the acquired ampC genes. The bla CMY-2-like genes were associated with ISEcp1; the surrounding bla DHA genes were similar to Klebsiella pneumoniae plasmid pTN60013 associated with IS26 and the psp and sap operons; and the bla ACC-1 genes were associated with IS26 elements inserted into ISEcp1. All of the carbapenemase genes (bla VIM-1, bla IMP-22, and bla IMP-28) were located in class 1 integrons. Therefore, although plasmids are the main cause of the rapid dissemination of ampC genes among Enterobacteriaceae, we need to be aware that other mobile genetic elements, such as insertion sequences, transposons, or integrons, can be involved in the mobilization of these genes of chromosomal origin. Additionally, three new integrons (In846 to In848) are described in this study.


Subject(s)
Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Enterobacteriaceae/enzymology , Plasmids/genetics , beta-Lactamases/genetics , beta-Lactamases/metabolism , Integrons/genetics , Spain
5.
Eur J Clin Microbiol Infect Dis ; 32(2): 253-9, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22956023

ABSTRACT

The purpose of this investigation was to determine the prevalence of plasmid-mediated AmpC (pAmpC) and carbapenemases in Enterobacteriaceae collected from 35 hospitals in Spain and to establish their epidemiological relationships. We conducted a prospective multi-centre study on pAmpC- or carbapenemase-producing Enterobacteriaceae isolates from clinical samples collected from February to July 2009. The strains suspected to carry pAmpC were resistant or showed intermediate susceptibility to co-amoxiclav and second- or third-generation cephalosporins. Strains suspected to carry a carbapenemase were selected because they showed a minimum inhibitory concentration (MIC) to imipenem >1 mg/L. Polymerase chain reaction (PCR) and a sequencing strategy were used to characterise the enzymes. The clonal relationships between isolates was analysed by pulsed field gel electrophoresis (PFGE). Among 100,132 Enterobacteriaceae isolates collected, 1,654 were compatible with the production of pAmpC or carbapenemases. We found a prevalence of 0.64 % of pAmpC (n = 635) and 0.04 % of carbapenemases (n = 43). The most prevalent pAmpC enzymes were CMY-type (78.3 %), DHA-type (19.5 %), ACC-type (1.6 %) and FOX-type (0.6 %). The CMY-type was the most frequent in Escherichia coli and Proteus mirabilis species, whereas the DHA-type was mainly found in Klebsiella spp. The enzymes involved in carbapenem resistance were VIM-1, IMP-22 and the new IMP-28. Nine new bla genes were described: bla (CMY-54), bla (CMY-55), bla (CMY-56), bla (CMY-57), bla (CMY-96), bla (DHA-6), bla (DHA-7), bla (FOX-8) and bla (IMP-28). The prevalence of pAmpC or carbapenemases found is not negligible. The CMY-types were the predominant pAmpC, whereas the VIM or IMP enzymes were the predominant carbapenemases. Furthermore, we observed a great genetic diversity among pAmpC-producing strains and a close clonal relationship between carbapenemase-producing strains.


Subject(s)
Cross Infection/epidemiology , Enterobacteriaceae Infections/epidemiology , Enterobacteriaceae Infections/microbiology , Enterobacteriaceae/enzymology , beta-Lactamases/genetics , Anti-Bacterial Agents/pharmacology , Cross Infection/microbiology , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , Electrophoresis, Gel, Pulsed-Field , Enterobacteriaceae/classification , Enterobacteriaceae/genetics , Enterobacteriaceae/isolation & purification , Genotype , Hospitals , Humans , Microbial Sensitivity Tests , Molecular Epidemiology , Plasmids/analysis , Polymerase Chain Reaction , Prevalence , Prospective Studies , Sequence Analysis, DNA , Spain/epidemiology , beta-Lactamases/metabolism
6.
Med. clín (Ed. impr.) ; 135(7): 300-305, sept. 2010. tab
Article in Spanish | IBECS | ID: ibc-83611

ABSTRACT

Fundamento y objetivoLa enfermedad de Fabry (EF) es una enfermedad hereditaria con manifestaciones clínicas multisistémicas.Fundamento y objetivoEl diagnóstico suele ser tardío, por lo que la afectación orgánica puede ser irreversible. La detección precoz de la enfermedad, en especial la afectación cardiaca, es crucial para que los pacientes puedan beneficiarse del tratamiento de reemplazo enzimático.Fundamento y objetivoEl objetivo de este estudio fue valorar si la resonancia magnética con secuencia de realce tardío con gadolinio puede ser útil para la detección precoz de la afectación cardiaca.Pacientes y métodosSe estudió a 20 pacientes (9 varones) con diagnóstico de EF a quienes se les realizó ecografía, Doppler tisular (DTI) y resonancia magnética.Pacientes y métodosSe consideró hipertrofia un grosor del septo y la pared posterior mayor o igual a 12mm. El DTI fue alterado con una velocidad de las ondas sistólicas, las ondas diastólicas tempranas o las ondas diastólicas tardías del anillo septal y lateral menor de 8cm/s.Pacientes y métodosSe realizó la resonancia magnética con secuencias de realce tardío con gadolinio.ResultadosLos pacientes incluidos se dividieron en 3 grupos según los resultados obtenidos: 1) DTI normal, sin hipertrofia del ventrículo izquierdo (HVI) 2) DTI alterado, sin HVI 3) DTI alterado e HVIResultadosLa resonancia detectó realce tardío en un paciente (DTI alterado e HVI).ConclusionesEl DTI es la única herramienta de diagnóstico precoz de afectación cardiaca en la EF. La resonancia magnética podría ser de gran valor para la estratificación diagnóstica.


Background and objectivesEarly detection of cardiac symptoms is of major interest in Fabry's disease (FD) in order to gain access to enzyme replacement therapy. Echo-Doppler tissular imaging (TDI) has been used as a cardiologic early marker in FD.ObjectivesThis study is intended to determine whether the cardiac magnetic resonance is as useful tool as TDI for the early detection of cardiac affectation in FD.Patients and methodsEchocardiography, tissue Doppler and Cardio magnetic resonance was performed in 20 patients with confirmed Fabry Disease.Patients and methodsLeft ventricular hypertrophy was defined as septum and left ventricular posterior wall thickness ≥12mm.Patients and methodsAn abnormal TDI velocity was defined as (Sa), (Ea) and/or (Aa) velocities <8cm/s at either the septal or lateral corner.ResultsTwenty patients included in the study were divided into three groups: 1. Those without left ventricular hypertrophy nor tissue Doppler impairment 2. Those without left ventricular hypertrophy and tissue Doppler impairment 3. Those with left ventricular hypertrophy and Tissue Doppler impairment.ResultsLate gadolinium enhancement was found in only one patient, who has already altered DTI and LVH.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Fabry Disease/complications , Magnetic Resonance Spectroscopy , Hypertrophy, Left Ventricular/diagnosis , Fabry Disease/diagnosis , Gadolinium , Hypertrophy, Left Ventricular/etiology
7.
Clin Microbiol Infect ; 16(9): 1482-7, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20002107

ABSTRACT

Chronic respiratory infection caused by Pseudomonas aeruginosa is the main driver of morbidity and mortality in cystic fibrosis (CF) patients. The development of resistance to all available antibiotics is a frequent outcome of these infections. The present study aimed to evaluate the activity of the new cephalosporin CXA-101 (FR264205) against a collection of 100 isolates obtained from 50 CF patients from two Spanish hospitals. The collection included the first (early) and the last (late) available isolate from each patient (average interval 68 ± 39 months). The MIC50 and MIC90 of CXA-101 were 0.5 and 2 mg/L and the geometric mean MIC was 0.7 mg/L; the MICs for 95% of the isolates were ≤8 mg/L (tentative breakpoint). Only meropenem yielded comparable results, although the MIC90 of this antibiotic was significantly higher (8 mg/L). CXA-101 showed conserved activity against a high proportion of isolates resistant to each of the antibiotics tested (ceftazidime, cefepime, piperacillin-tazobactam, imipenem, meropenem, levofloxacin and tobramycin), with MIC50 values of 1-2 mg/L. Moreover, CXA-101 retained good activity against multidrug-resistant strains, with MIC50 and MIC90 values of 2 and 16 mg/L. CXA-101 was also active against late CF isolates (the MIC for 96% was ≤8 mg/L); it was the only antibiotic tested to which a similar percentage of early and late isolates was susceptible. These results show that, despite a slight increase in MICs, major cross-resistance to CXA-101 did not develop during treatment of CF patients with the currently available antipseudomonal agents. Therefore, CXA-101 is envisaged as a valuable alternative for the treatment of chronic respiratory infection caused by P. aeruginosa in CF patients.


Subject(s)
Anti-Bacterial Agents/pharmacology , Cephalosporins/pharmacology , Cystic Fibrosis/complications , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/drug effects , Drug Resistance, Multiple, Bacterial , Hospitals , Humans , Microbial Sensitivity Tests , Pseudomonas aeruginosa/isolation & purification , Spain , beta-Lactam Resistance
8.
Antimicrob Agents Chemother ; 53(12): 5288-90, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19770278

ABSTRACT

Two clonally related Pseudomonas aeruginosa isolates, recovered from two patients admitted to a pediatric intensive care unit, were found to harbor a new OXA-2 variant (Asn148Asp), designated OXA-161. The plasmid location of bla(OXA-161) was demonstrated through electroporation to PAO1, and its codification in a class I integron (together with aacA4) was demonstrated through PCR and sequencing. bla(OXA-2) and bla(OXA-161) were cloned in parallel to demonstrate the extended-spectrum beta-lactamase properties of OXA-161, conferring resistance to ceftazidime and reduced susceptibility to cefepime and aztreonam.


Subject(s)
Integrons/genetics , Plasmids/genetics , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/enzymology , Pseudomonas aeruginosa/genetics , beta-Lactamases/genetics , Amikacin/pharmacology , Aminoglycosides/pharmacology , Anti-Bacterial Agents/pharmacology , Cefepime , Cephalosporins/pharmacology , Clavulanic Acid/pharmacology , Gentamicins/pharmacology , Humans , Imipenem/pharmacology , Meropenem , Molecular Sequence Data , Penicillanic Acid/analogs & derivatives , Penicillanic Acid/pharmacology , Piperacillin/pharmacology , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/isolation & purification , Spain , Tazobactam , Thienamycins/pharmacology
9.
Int J Gynecol Cancer ; 15(5): 938-45, 2005.
Article in English | MEDLINE | ID: mdl-16174249

ABSTRACT

Daily diet factors that could potentially be related to endometrial cancer (EC) in Mexico are still unknown. This study aims to evaluate the association between EC and Mexican dietary factors. A case-control study in Mexico City was conducted during 1995-1997 in a social security hospital, using 85 incident cases of EC and 629 controls. A validated questionnaire with 116 items about the frequency and type of food intake was used. The analysis of nutrients was performed using the residual method, adjusting by predictor variables through logistic regression methods. In addition, partitional models estimated total caloric intake for other sources. We found no association between EC risk and consumption of animal or vegetable proteins, saturated, monounsaturated, or polyunsaturated fat, although high intake of nutrients such as lactose (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.21-1.01, P for trend = 0.004), vitamin D (OR, 0.38; 95% CI, 0.18-0.82, P= 0.003), and calcium (OR, 0.39; 95% CI, 0.17-0.89, P= 0.02) were inversely associated with EC. Our results suggest that dietary vitamin D and calcium play an important role in the development of EC, although the mechanisms postulated should be explained with additional studies with large populations.


Subject(s)
Diet , Endometrial Neoplasms/epidemiology , Endometrial Neoplasms/etiology , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Endometrial Neoplasms/prevention & control , Energy Intake , Feeding Behavior , Female , Humans , Logistic Models , Mexico/epidemiology , Middle Aged , Risk Factors , Surveys and Questionnaires
10.
Int J Med Robot ; 1(1): 7-22, 2004 Jun.
Article in English | MEDLINE | ID: mdl-17520593

ABSTRACT

The use of robotic technologies to assist surgeons was conceptually described almost thirty years ago but has only recently become feasible. In Neurosurgery, medical robots have been applied to neurosurgery for over 19 years. Nevertheless this field remains unknown to most neurosurgeons. The intrinsic characteristics of robots, such as high precision, repeatability and endurance make them ideal surgeon's assistants. Unfortunately, limitations in the current available systems make its use limited to very few centers in the world. During the last decade, important efforts have been made between academic and industry partnerships to develop robots suitable for use in the operating room environment. Although some applications have been successful in areas of laparoscopic surgery and orthopaedics, Neurosurgery has presented a major challenge due to the eloquence of the surrounding anatomy. This review focuses on the application of medical robotics in neurosurgery. The paper begins with an overview of the development of the medical robotics, followed by the current clinical applications in neurosurgery and an analysis of current limitations. We discuss robotic applications based in our own experience in the field. Next, we discuss the technological challenges and research areas to overcome those limitations, including some of our current research approaches for future progress in the field.


Subject(s)
Neurosurgical Procedures/methods , Robotics , Equipment Design , History, 20th Century , History, 21st Century , Humans , Neurosurgical Procedures/instrumentation , Neurosurgical Procedures/trends , Robotics/classification , Robotics/history , Robotics/instrumentation , Robotics/trends
11.
Int J Gynecol Cancer ; 13(6): 756-63, 2003.
Article in English | MEDLINE | ID: mdl-14675311

ABSTRACT

The purpose of this study was to identify risk factors associated with the development of non-epithelial ovarian cancer in Mexican women. A case-control study was carried out on women registered with the Mexican Institute of Social Security in Mexico City over a period of two years (1995-97). Twenty-eight new cases were recruited from the Gynecology and Obstetrics Hospital no. 4, "Luis Castelazo Ayala", and were matched by age with 84 controls selected randomly. Eighteen (64.3%) cases of germ cell tumors and 10 (35.7%) stromal sex cord tumors were found. The number of full term pregnancies was associated inversely to development of stromal sex cord tumors with lower risk in women with more than three full term pregnancies (odds ratio, 0.02: 95% confidence interval, 0.001-0.56) compared to nulliparous women. No associations were found respecting to germ cell tumors. Parity was inversely associated to development of stromal sex cord tumors, probably as a result of the endocrine system's influence on the ovaries. The development of germ cell tumors could be associated to factors not evaluated in this study.


Subject(s)
Carcinoma/ethnology , Carcinoma/etiology , Neoplasms, Germ Cell and Embryonal/ethnology , Neoplasms, Germ Cell and Embryonal/etiology , Ovarian Neoplasms/ethnology , Ovarian Neoplasms/etiology , Pregnancy , Adolescent , Adult , Age Factors , Aged , Carcinoma/prevention & control , Case-Control Studies , Child , Female , Humans , Mexico/ethnology , Middle Aged , Neoplasms, Germ Cell and Embryonal/prevention & control , Odds Ratio , Ovarian Neoplasms/prevention & control , Parity , Risk Factors , Stromal Cells
12.
Minim Invasive Neurosurg ; 46(4): 193-7, 2003 Aug.
Article in English | MEDLINE | ID: mdl-14506560

ABSTRACT

OBJECT: Image guidance provides a three-dimensional view of the lesion and allows the surgeon to plan a surgical strategy that takes the relationship of the lesion and the surrounding brain into account. We evaluated the degree of resection and the functional outcome of patients with colloid cysts from the third ventricle submitted to surgical resection using interactive image-guided approach. METHOD: Using image-guided methodology and an endoscopic approach we analyzed the functional outcome of 11 patients with diagnosis of colloid cyst of the third ventricle who were treated at our institution from August 1993 to September 2000. The mean age was 39.5 years and the mean follow-up was 36.5 months. Analyzing the clinical outcome, 54.5% of the patients developed short-term memory disturbance in the first 30 days after surgery. None of these patients persisted with this symptomatology for more than one month. In terms of late post-operative morbidity, 1 patient developed persistent post-operative seizures, which were controlled with anti-seizure medications. Complete resection of the cyst was achieved in all patients. CONCLUSIONS: The low rate of complications and high rate of total resection encourage us to continue using the multimodal technique. Longer follow-up and an increase in the number of patients are needed to assess the efficacy of this methodology.


Subject(s)
Brain Diseases/surgery , Cysts/surgery , Endoscopy/methods , Neurosurgical Procedures/methods , Surgery, Computer-Assisted , Third Ventricle/surgery , Adolescent , Adult , Female , Humans , Male , Memory Disorders/etiology , Middle Aged , Neurosurgical Procedures/adverse effects , Retrospective Studies , Third Ventricle/pathology , Treatment Outcome
13.
Int J Radiat Oncol Biol Phys ; 51(4): 963-8, 2001 Nov 15.
Article in English | MEDLINE | ID: mdl-11704318

ABSTRACT

PURPOSE: When an initial retrospective review of malignant glioma patients (MG) undergoing brachytherapy was carried out using the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) criteria, it revealed that glioblastoma multiforme (GBM) cases benefit the most from implant. In the present study, we focused exclusively on these GBM patients stratified by RPA survival class and looked at the relationship between survival and implanted target volume, to distinguish the prognostic value of volume in general and for a given GBM class. METHODS AND MATERIALS: Between 1991 and 1998, 75 MG patients were treated with surgery, external beam radiation, and stereotactic iodine-125 (I-125) implant. Of these, 53 patients (70.7%) had GBMs, with 52 (98%) having target volume (TV) data for analysis. Stratification by RPA criteria showed 12, 26, 13, and 1 patients in classes III to VI, respectively. For analysis purposes, classes V and VI were merged. There were 27 (51.9%) male and 25 (48.1%) female patients. Mean age was 57.5 years (range 14-79). Median Karnofsky performance status (KPS) was 90 (range 50-100). Median follow-up time was 11 months (range 2-79). RESULTS: At analysis, 18 GBM patients (34.6%) were alive and 34 (65.4%) were dead. Two-year and 5-year survivals were 42% and 17.5%, respectively, with a median survival time (MST) of 16 months. Two-year survivals and MSTs for the implanted GBM patients compared to the RTOG database were as follows: 74% vs. 35% and 28 months vs. 17.9 months for class III; 32% vs. 15% and 16 months vs. 11.1 months for class IV; 29% vs. 6% and 11 months vs. 8.9 months for class V/VI. Mean implanted TV was 15.5 cc (range 0.8-78), which corresponds to a spherical implant diameter of 3.1 cm. Plotting survival as a function of 5-cc TV increments suggested a trend toward poorer survival as the implanted volume increases. The impact of incremental changes in TV on survival within a given RPA class of GBMs was compared to the RTOG database. Looking at absolute differences in MSTs: for classes III and IV, there was little effect of different TVs on survival; for class V/VI, a survival benefit to implantation was still seen at the target volume cutoff (TV > 25 cc). Within a given RPA class, no significant differences were found within class III; for class IV, the most significant difference was at 10 cc (p = 0.05); and for class V/VI, at 20 cc (p = 0.06). CONCLUSION: For all GBM patients, an inverse relationship between implanted TV size and median survival is suggested by this study. However, when GBM patients are stratified using the RTOG's RPA criteria, the prognostic effect of implant volume disappears within each RPA survival class. At the critical volume of 25 cc, which approximates an implant of 5-cm diameter (upper implantation limit of many CNS brachytherapy protocols), the "poorest" prognosis GBM patients stratified by RPA still demonstrate a survival benefit with implant. We suggest that any GBM patient meeting brachytherapy recognized size criteria be considered for I-125 implant.


Subject(s)
Brachytherapy , Brain Neoplasms/mortality , Brain Neoplasms/radiotherapy , Glioblastoma/mortality , Glioblastoma/radiotherapy , Adolescent , Adult , Aged , Decision Making , Female , Follow-Up Studies , Humans , Iodine Radioisotopes/therapeutic use , Male , Middle Aged , Patient Selection , Prognosis , Radiopharmaceuticals/therapeutic use , Retrospective Studies , Survival Analysis
15.
Neurosurg Focus ; 9(6): e9, 2000 Dec 15.
Article in English | MEDLINE | ID: mdl-16817692

ABSTRACT

OBJECT: This trial was designed to determine the ability of autologous whole-tumor cell vaccines to induce cell mediated immune responses in patients with recurrent malignant glioma, as well as to determine whether combining such vaccination with adoptive transfer of in vitro activated T lymphocytes prolongs patient survival. METHODS: Nineteen patients with recurrent malignant glioma, in whom previous external beam radiotherapy and at least one course of chemotherapy had failed were vaccinated twice with irradiated autologous whole tumor cells by using granulocyte-marcrophage colony-stimulating factor as an adjuvant. Patients then underwent leukapheresis followed by adoptive transfer of peripheral blood lymphocytes activated in vitro with anti-CD3 and interleukin-2. In vivo immune response, radiological response, clinical outcome, and survival were monitored. Seventeen patients developed a delayed-type hypersensitivity (DTH) response to vaccination that appeared to be directed against the autologous tumor. In eight patients there was radiological evidence of a response and in five there was evidence of clinical improvement. Median survival was 12 months (range 6-28 months), and both the presence of a DTH response and the radiological response correlated with survival (p < 0.02 and p < 0.04, respectively). CONCLUSIONS: These preliminary results suggest that autologous whole-tumor cell vaccines induce a cell-mediated immune response, which appears to be tumor specific in most patients. Furthermore, vaccination combined with adoptive immunotherapy with in vitro activated cells may induce a radiologically demonstrated tumor response and improved survival despite a condition of advanced disease and immunosuppression resulting from previous treatment or tumor burden. Further studies of immunotherapy are warranted.


Subject(s)
Brain Neoplasms/therapy , CD3 Complex/immunology , Cancer Vaccines/administration & dosage , Glioma/therapy , Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage , Immunotherapy, Adoptive/methods , Adjuvants, Immunologic/administration & dosage , Adult , Aged , Brain Neoplasms/immunology , Brain Neoplasms/pathology , Cancer Vaccines/adverse effects , Female , Glioma/immunology , Glioma/pathology , Humans , Immunotherapy, Adoptive/adverse effects , Leukapheresis , Lymphocyte Activation/immunology , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Recurrence, Local/immunology , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Survival Rate , T-Lymphocytes/immunology , Treatment Outcome
16.
Int J Radiat Oncol Biol Phys ; 45(3): 687-92, 1999 Oct 01.
Article in English | MEDLINE | ID: mdl-10524423

ABSTRACT

PURPOSE: To date, numerous retrospective studies have suggested that the addition of brachytherapy to the conventional treatment of malignant gliomas (MG) (surgical resection followed by radiotherapy +/- chemotherapy) leads to improvements in survival. Two randomized trials have suggested either a positive or no survival benefit with implants. Critics of retrospective reports have suggested that the improvement in patient survival is due to selection bias. A recursive analysis by the RTOG of MG trials has stratified MG patients into 6 prognostically significant classes. We used the RTOG criteria to analyze the implant data at Wayne State University to determine the impact of selection bias. METHODS AND MATERIALS: Between July 1991 and January 1998, 75 patients were treated with a combination of surgery, radiotherapy, and stereotactic I-125 implant as primary MG management. Forty-one (54.7%) were male; 34 (45.3%) female. Median age was 52 years (range 4-79). Twenty-two (29.3%) had anaplastic astrocytoma (AA); 53 (70.7%), glioblastoma multiforme (GBM). Seventy-two patients had data making them eligible for stratification into the 6 RTOG prognostic classes (I-VI). Median Karnofsky performance status (KPS) was 90 (range 50-100). There were 14, 0, 14, 31, 12, and 1 patients in Classes I to VI, respectively. Median follow-up time for AA, GBM, and any surviving patient was 29, 12.5, and 35 months, respectively. RESULTS: At analysis, 29 (40.3%) patients were alive; 43 (59.7%), dead. For AA and GBM patients, 2-year and median survivals were: 58% and 40%; 38 and 17 months, respectively. For analysis purposes, Classes I and II, V and VI were merged. By class, the 2-year survival for implanted patients compared to the RTOG data base was: III--68% vs. I--76%; III--74% vs. 35%; IV--34% vs. 15%; V/VI--29% vs. V--6%. For implant patients, median survival by class was (in months): I/II--37; III--31; IV--16; V/VI--11. CONCLUSION: When applied to MG patients receiving permanent I-125 implant, the criteria of the RTOG recursive partitioning analysis are a valid tool to define prognostically distinct survival groups. As reflected in the RTOG study, a downward survival trend for the implant patients is seen from "best to worse" class patients. Compared to the RTOG database, median survival achieved by the addition of implant is improved most demonstrably for the poorer prognostic classes. This would suggest that selection bias alone does not account for the survival benefit seen with I-125 implant and would contradict the notion that the patients most eligible for implant are those gaining the most benefit from the treatment. In light of the contradictory results from two randomized studies and given the present results, further randomized studies with effective stratification are required since the evidence for a survival benefit with brachytherapy (as seen in retrospective studies) is substantial.


Subject(s)
Brain Neoplasms/radiotherapy , Glioma/radiotherapy , Iodine Radioisotopes/therapeutic use , Radiopharmaceuticals/therapeutic use , Adolescent , Adult , Aged , Bias , Brachytherapy , Brain Neoplasms/mortality , Brain Neoplasms/surgery , Child , Child, Preschool , Combined Modality Therapy , Female , Glioma/mortality , Glioma/surgery , Humans , Male , Middle Aged , Patient Selection , Prognosis , Retrospective Studies , Survival Analysis
17.
Int J Radiat Oncol Biol Phys ; 43(5): 977-82, 1999 Mar 15.
Article in English | MEDLINE | ID: mdl-10192343

ABSTRACT

PURPOSE: To determine the efficacy and toxicity of permanent 125iodine implants for recurrent malignant gliomas. METHODS AND MATERIALS: Between January 1989 and January:, 59 patients with histologically confirmed recurrent malignant gliomas (22 nonglioblastoma malignant gliomas, 37 glioblastoma multiforme at the time of implant) received a permanent 125iodine implant. Patients ranged in age from 13-74 years. The median ages for the overall group, nonglioblastoma (nonGBM), and glioblastoma (GBM) groups was 47 years, 39 years, and 53 years, respectively. RESULTS: With a median follow-up of 40 months, the median survival for the 59 total patients is 1.34 years; nonGBM 2.04 years, GBM 0.9 years. Factors predictive for poor prognosis were GBM histology, age 60 years or more, target volume 17 cc or more, and/or tumor location within the corpus callosum or thalamus. Reoperations have been performed in 24 (40%) patients; 15 (25%) for tumor progression; 3 (5%) for radiation necrosis; 2 (3%) for skull necrosis/infection, and 4 (7%) for other reasons (Ommaya reservoir insertion, catheter removal, hematoma evacuation). CONCLUSION: Permanent 125iodine implants in selected patients with recurrent malignant gliomas are associated with reasonable long-term survival and a low risk of complications. Given the low incidence of radiation necrosis, future plans are to increase dose rate and/or total dose delivered with the permanent implant.


Subject(s)
Brain Neoplasms/radiotherapy , Glioma/radiotherapy , Iodine Radioisotopes/therapeutic use , Neoplasm Recurrence, Local/radiotherapy , Radiopharmaceuticals/therapeutic use , Adolescent , Adult , Aged , Brain Neoplasms/mortality , Female , Follow-Up Studies , Glioma/mortality , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Survival Analysis
18.
Comput Aided Surg ; 4(6): 314-21, 1999.
Article in English | MEDLINE | ID: mdl-10631374

ABSTRACT

Application accuracy is a crucial factor for stereotactic surgical localization systems, in which space digitization camera systems are one of the most critical components. In this study we compared the effect of the OPTOTRAK 3020 space digitization system and the FlashPoint Model 3000 and 5000 3D digitizer systems on the application accuracy for interactive localization of intracranial lesions. A phantom was mounted with several implantable frameless markers which were randomly distributed on its surface. The target point was digitized and the coordinates were recorded and compared with reference points. The differences from the reference points represented the deviation from the "true point." The root mean square (RMS) was calculated to show the differences, and a paired t-test was used to analyze the results. The results with the phantom showed that, for 1-mm sections of CT scans, the RMS was 0.76 +/- 0. 54 mm for the OPTOTRAK system, 1.23 +/- 0.53 mm for the FlashPoint Model 3000 3D digitizer system, and 1.00 +/- 0.42 mm for the FlashPoint Model 5000 system. These preliminary results showed that there is no significant difference between the three tracking systems, and, from the quality point of view, they can all be used for image-guided surgery procedures.


Subject(s)
Phantoms, Imaging , Stereotaxic Techniques/instrumentation , Equipment Design , Humans , Reproducibility of Results
19.
Rev Med Chil ; 126(8): 1010-8, 1998 Aug.
Article in Spanish | MEDLINE | ID: mdl-9830755

ABSTRACT

BACKGROUND: Despite the epidemiological importance and the surveillance programs to detect cervix uterine cancer in Chile, its mortality continues to be high. AIM: To perform an audit of all deaths due to cervix uterine cancer, that occurred in a health service of Santiago during 1995. MATERIAL AND METHODS: The clinical records and pathological studies of 46 women, whose death certificates indicated cervix uterine cancer as the cause of death, were audited. RESULTS: In six women, the audit revealed that the cause of death was not a cervix uterine cancer, and they were discarded from further analyses. The higher mortality rate (36/100,000) occurred in women over 64 years old, those living in the poorest community and with less Papanicolaou vaginal smears coverage (La Pintana). The evolution prior to diagnosis was registered in only four women and was of less than one year. Most women consulted in advanced stages of the disease and only 48% were subjected to some sort of treatment (surgery, radiotherapy or chemotherapy). Mean survival was 3 years and mean age at death was 55.5 years old. There was a great lack of clinical and epidemiological information. In only 13 women information about previous Pap smears was registered. CONCLUSIONS: Audit of deaths should be an important component of preventive programs for cervix uterine cancer, and the coverage of Pap smears should be improved.


Subject(s)
Uterine Cervical Neoplasms/mortality , Adult , Age Distribution , Age Factors , Aged , Cause of Death , Chile , Female , Humans , Medical Audit , Middle Aged , Papanicolaou Test , Survival Rate , Urban Health Services/statistics & numerical data , Vaginal Smears/statistics & numerical data
20.
Minim Invasive Neurosurg ; 41(3): 166-71, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9802042

ABSTRACT

Anterior decompressive procedures for the treatment of vertebral tumors have become increasingly popular in an attempt to improve the quality of life, relieve pain, and preserve or restore neurologic function. However, these procedures carry a significant rate of complications including hardware failure, due in part to technical factors. A computer-assisted system allowing for precise preoperative planning and real-time intraoperative interactive image localization has been implemented for spine instrumentation to optimize anterior instrumental fixation. We discuss our initial clinical experience and application to anterior vertebrectomy, and vertebral reconstruction with anterior instrumental fixation. We believe that computer-assisted spine surgery using infrared-based technology offers the necessary elements to make its use fast, reliable, and intuitive, providing an accurate and safe approach for optimization of spine surgery.


Subject(s)
Decompression, Surgical/instrumentation , Image Processing, Computer-Assisted/instrumentation , Laminectomy/instrumentation , Spinal Fractures/surgery , Spinal Fusion/instrumentation , Spinal Neoplasms/surgery , Adult , Aged , Equipment Design , Humans , Lumbar Vertebrae/surgery , Male , Spinal Cord Compression/diagnosis , Spinal Cord Compression/surgery , Spinal Fractures/diagnosis , Spinal Neoplasms/diagnosis , Surgical Instruments , Thoracic Vertebrae/surgery , Tomography, X-Ray Computed/instrumentation
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