Synthesis and characterization of lanthanum phosphate nanoparticles as carriers for (223)Ra and (225)Ra for targeted alpha therapy.

INTRODUCTION: Targeted alpha therapy (TAT) has the potential for killing micro-metastases with minimum collateral damage to surrounding healthy tissue. In-vivo generator radionuclides, such as(223)Ra, (225)Ra, and (225)Ac, are of special interest for radiotherapeutic applications as they emit multiple α-particles during their decay. Utilizing appropriate carriers capable of retaining both the parent radioisotope as well as daughter products is important for the effective delivery of the radioisotope to the tumor site while mitigating global in vivo radiotoxicity. In this work, LaPO4 core and core+2 shells nanoparticles (NPs) (NPs with 2 layers of cold LaPO4 deposited on the core surfaces) were synthesized containing either (223)Ra or(225)Ra/(225)Ac, and the retention of the parents and daughters within the NPs in vitro was investigated. METHODS: Core LaPO4 NPs were synthesized in aqueous solution by reacting 1 equivalent of La(NO3)3, along with few microcuries of either (223)Ra or (225)Ra/(225)Ac, with 1 equivalent of sodium tripolyphosphate (TPP) under moderate heating and purified by membrane dialysis. Core-shell NPs were also synthesized with one (core+1 shell) and two (core+2 shells) cold LaPO4 layers deposited onto the radioactive cores. The NPs were then characterized by transmission electron microscopy (TEM) and powder x-ray diffraction (XRD). Identification and quantification of radioactive parents and daughters released from the NPs in vitro were investigated using gamma-ray spectroscopy. RESULTS: XRD and TEM analysis revealed that the NPs crystallized in the rhabdophane phase with mean diameters of 3.4 and 6.3nm for core and core+2 shells, respectively. The core LaPO4 NPs retained up to 88% of (223)Ra over 35days. However, in the core+2 shells NPs, the retention of (223)Ra and its daughter, (211)Pb, was improved to >99.9% over 27days. Additionally, the retention of (225)Ra/(225)Ac parents was >99.98% and ~80% for the (221)Fr and (213)Bi daughters over 35days for the core+2 shells NPs. CONCLUSIONS: The in vitro retention of both parents and daughters results suggests that LaPO4 NPs are potentially effective carriers of radium isotopes.

[Cleidocranial dysostosis. Presentation of a case]. / Disostosis cleidocraneal. Presentación de un caso.

INTRODUCTION: Cleidocranial dysostosis is a syndrome defined by three characteristic findings: clavicular aplasia, retarded cranial ossification, and autosomic dominant hereditary transmission, with completed penetrance and full expression. However, the diagnosis cannot only be made based on those finding, because the polymorphism and extension of the lesions of this disease is important. Therefore, in this disease we can see upset in the second teething, short stature or dwarf, persistence of the biconvex appearance of vertebral body, bone hypoplastic iliac, retarded pubis branch ossification, wedge shape distal phalanges or with brachymesophalangia of the forefinger and fifth finger. CLINICAL CASE: We describe a 20 years old man, with cleidocranial dysostosis, without familiar antecedent (probable mutation), that come to our center for treatment of denture pathology with disabled eating, because anomalous distribution and eruption. He had clavicle agenesis, cranial ossification upset with wormian bones, vertebral bodies biconvex, superior maxillary hypoplastic, and dental packed in the superior maxillary and jawbone. CONCLUSIONS: Cleidocranial dysostosis is a hereditary disease, which can be of spontaneous apparition (mutation), has a grand polymorphism, affect the osseous development, predominate in the middle line membranous bone and is an entity of radiologic diagnosis.

[Severe craniocerebral injuries with a lucid interval]. / Traumatismos craneoencefálicos graves con intervalo lúcido.

Some variables were analyzed in 35 patients with severe cranioencephalic injuries following a lucid interval according to mortality. The variables analyzed were: age of less than 40 years, interval of time accident-admission (TAA), admission-operation (TAO), level of consciousness (Glasgow scale), associated extracranial lesions, type of intracranial lesion, and tomodensitometric signs of intracranial hypertension. The only variables demonstrating significant statistical differences (p < 0.05) were the level of consciousness (Glasgow scale < 6 points) and the presence of subdural hematoma. Twelve (70.5%) patients who died had less than 6 on the Glasgow scale and in contrast only 5 (27.7%) of the living. Eleven (64.7%) of the group who died and 4 (22.2%) of the living had subdural hematoma. These data suggest that the level of consciousness and the type of lesion are determining factors of the mortality in this type of patients. Early detection and energic treatment of secondary lesions contribute to prognostic improvement of cranioencephalic injuries.

[Predictive factors of mortality in severe craniocerebral trauma]. / Factores predictivos de la mortalidad en los traumatismos craneoencefálicos graves.

BACKGROUND: The prediction of mortality in severe head injury is of interest for the evaluation of patient prognosis and to also permit therapeutic measures to be considered and improve knowledge of this problem. METHODS: A multiple logistic regression model was developed and validated from the data obtained from a series of 231 patients hospitalized for the above mentioned condition. Seventy-five percent of the patients were used to define the model with the remaining 25% validating the same. RESULTS: The variables included in the model were: intraventricular hemorrhage, odds ratio = 20.4 (confidence interval 95%: 3.56-116); compression of basal cistern and/or of the III ventricle, odds ratio = 11.5 (4.43-29.8); mydriatic pupils in both eyes, odds ratio = 5.71 (1.32-24.6); age, odds ratio = 1.03 (1.01-1.05) and Glasgow scale upon admission, odds ratio = 0.57 (0.43-0.75). The maximum global value of the model (84.9%) corresponded to a sensitivity of 84.5% and specificity of 85.2%. The cut-off point of probability of death was found to be 0.475. In the validation of the model the highest global value (84.2%) was also observed at the cut-off point of 0.475 with a sensitivity of 84.2% and specificity of 84.4%. CONCLUSIONS: The predictive factors of mortality in severe head injury are the evidence of hemorrhage in the cerebral ventricles, mydriasis and a low score on the Glasgow scale. The model presented is useful and valid for carrying out the prediction of mortality at the time of admission and is also easy to apply since the variables used are obtained in the initial examination of the patients with severe head injury.

[Epidemiology of head traumas. "Barcelona" data base. Objectives, design and analysis of 584 cases]. / Epidemiología de los traumatismos craneoencefálicos. Banco de datos "Barcelona". Objetivos, diseño y análisis de 584 casos.

INTRODUCTION: Descriptive analysis of some features in patients with cranio-encephalic traumatisms (CET) admitted to our hospital and collected in a data base, in order to establish the prognosis of the lesions and apply the most appropriate diagnostic and therapeutic procedures. MATERIAL AND METHODS: Since July 1987 to June 1989 we collected data on 584 patients with CET who presented the following selection criteria: consciousness level lower than 13 points in the Glasgow scale and/or pathologic computerized tomography. According to the consciousness level (Glasgow scale) on admission, patients were classified into three groups: slight CET (Glasgow 15-13), moderate CET (Glasgow 12-9), and severe CET (Glasgow < 9). The traumatic mechanisms were divided into 8 categories (occupant, pedestrian, motorbike, aggression, labor, drop, sporting, cyclist). According to the main lesion we considered the following diagnoses: subdural hematoma, epidural hematoma, cerebral contusion (s), diffuse lesion with normal computerized tomography and/or subarachnoid hemorrhage, cerebral congestion, and diffuse axonal lesion. Results were evaluated six months after using the Glasgow scale. RESULTS: The mean age of patients with slight CET was 37.7 +/- 22.1 years, those with moderate CET 31.7 +/- 22.6 years, and those with severe CET 30.8 +/- 21.6 years. Four hundred and forty-two were men (75.6%). The time period between the accident and hospital admission could be determined in 512 cases (87.6%). Severe CET arrived to the hospital (4.8 +/- 7.3 hours) earlier than the other groups (6.6 +/- 11.9 hours in moderate CET and 14.2 +/- 23 hours in slight CET). Most of patients, 488 (83.5%), were referred from another hospital, whereas the remaining cases came directly from the accident place. Traumatic mechanisms according to the previous categories were: occupant 145 (25%), pedestrian 112 (20%), motorbike 104 (18%), cyclist 2 (0.003%), labor 39 (7%), drop 154 (27%), sporting 7 (1%), aggression 10 (2%). Percentage of traffic accident was higher in patients with severe CET (74.6, 64, and 47% in severe moderate, and slight CET, respectively). The main lesions were: acute subdural hematoma, 72 (12.3%); cerebral contusion, 207 (35.4%); epidural hematoma, 88 (15%); normal computerized tomography/subarachnoid hemorrhage, 87 (14.8%); swelling, 17 (2.9%); diffuse axonal injury, 74 (12.6%); and the remaining, 39 (6.6%) had other lesions such as hydrocephalus fracture-sinking, etc. Mortality was 44.2, 12.2, and 3.7% respectively in severe, moderate, and slight CET. CONCLUSIONS: Data base may contribute to establish the prognosis of CET and to determine the efficacy of therapeutic procedures as well as that of diagnostic and investigational methods.

[Intraventricular meningiomas]. / Meningiomas intraventriculares.

Eight cases of surgically intervened intraventricular meningiomas are presented. The patients were six males and 2 females with a mean age of 41.7 years (11-70). The length of symptoms was of several months in 6 (75%) of the cases. The most frequent symptoms observed were cephalea and alterations of the upper functions which were presented in six and four cases, respectively. Papilloedema and involvement of long pathways were the most usual findings observed in neurological examination. Diagnosis was made by computerized tomography and angiography in all the cases. Surgery using a transtemporal approach was carried out in six patients and in the other two a parietal-occipital route was used. Two patients were dead and other two presented bilateral amaurosis. The other patients had good postsurgery.

[Decrease in the incidence of epidural hematomas surgically treated during coma after a lucid interval. Is this an index of quality of care?]. / Disminución de la incidencia de hematomas epidurales intervenidos en coma después de un intervalo lúcido. Es un índice de la calidad asistencial?

The level of consciousness prior to surgery has been analyzed in a series of 64 patients suffering epidural hematoma (EDH) who underwent surgery during the period from July 1987 to June 1989. The percentage of cases which underwent surgery in coma after a lucid interval have been compared in different periods of time (1978-80, 1981-82, 1983-84 and July 1987 to June 1989). During the period from July 1987 to June 1989 surgery was performed on: 15 patients (23.5%) in coma from the moment of accident, 8 patients (12.5%) underwent surgery in coma but after a lucid interval and 41 patients (64.1%) were conscious. During the different periods of time the number of patients undergoing surgery in coma after a lucid interval were the following: 1979-80, 9 cases (26.5%); 1981-82, 17 cases (43.6%); 1983-84, 8 cases (20%) and during the last period, 1987-89, 7 cases (15.2%). The difference between the percentage of patients intervened in coma after a lucid interval in the previously referred periods of time was statistically significant (p 0.05).

[Reduction of the mortality from acute subdural hematoma. Comparison of 2 series (1979-1982 and 1987-1989) of patients operated on at the Hospital de la Vall d'Hebron]. / Reducción de la mortalidad en el hematoma subdural agudo. Comparación de dos series (1979-1982 y 1987-1989) de pacientes intervenidos en el Hospital de la Vall d'Hebron.

Several clinical variables from a series of 101 patients with acute subdural hematoma (ASDH) operated on during the period 1979-1989 were compared with those from another group of 43 patients who were operated on during the period 1987-1989. Twenty-seven patients (26.7%) in the earlier period and 15 (34.8%) in the later one were younger than 40 years. The difference was not significant. There was a higher proportion of patients, 41 (40.5%), in the earlier period (1979-1982) who had traffic accidents than in the 1987-1989 period, where trauma was the mechanism in 15 patients (38.8%). However, the difference was not significant. Seven patients (6.9%) from the earlier group and 18 (41.9%) from the later group had a lucid interval. This difference was significant (p less than 0.001). During the 1979-1982 period 80 patients (79.2%) were comatose on admission as compared with 27 (62.7%) during 1987-1989. The difference was significant (p less than 0.05). A small group of 11 patients (10.8%) from the earlier series were operated on by means of craniotomy or trephine; by contrast, this approach was used in 35 (81.3%) patients from the later series. The difference was significant (p less than 0.001). Seventy-nine (78.2%) and 26 (60.4%) patients died in the periods 1979-1982 and 1987-1989, respectively. The difference between the mortality rates of both groups were significant (p less than 0.05). Our data suggest that the earlier diagnosis and the use of wider surgical procedures have contributed to the reduction in mortality.

[Symptomatic chronic subdural hematoma. Analysis of 68 cases treated surgically with small craniotomy and placement of a closed drainage system]. / Hematoma subdural crónico sintomático. Análisis de 68 casos tratados quirúrgicamente con pequeña craneostomía y colocación de sistema de drenaje cerrado.

Sixty eight cases of chronic subdural hematoma (CSDH) surgically treated (December 1984-December 1988) with twist drill craniostomy (3-4 mm) and application of a closed drainage system (CDS) are reviewed. The patients were distributed in four groups depending on the density of the hematoma: hypodense (36 cases), isodense (6 cases), of mixed density (22 cases) and hyperdense (4 cases). In about one third of patients (25 cases) the duration of symptoms was shorter than one week, in 21 cases it was between one week and one month, and in 22 patients it was longer than one month. 77.95% of cases had a preceding head injury. Headache and motor deficits were the leading symptoms, being present in 43 (63.2%) and 42 (61.7%) cases, respectively. Twelve patients (17.6%) were comatose on admission. Twelve patients required reoperation. Six patients died (8.8%). The preoperative neurological status and associated systemic diseases influenced the outcome. We think that limited craniostomy with CDS is the therapy of choice for symptomatic CSDH.