Metal Ion Binding in Wild-Type and Mutated Frataxin: A Stability Study.

This work studies the stability of wild-type frataxin and some of its variants found in cancer tissues upon Co2+ binding. Although the physiologically involved metal ion in the frataxin enzymatic activity is Fe2+, as it is customarily done, Co2+ is most often used in experiments because Fe2+ is extremely unstable owing to the fast oxidation reaction Fe2+ → Fe3+. Protein stability is monitored following the conformational changes induced by Co2+ binding as measured by circular dichroism, fluorescence spectroscopy, and melting temperature measurements. The stability ranking among the wild-type frataxin and its variants obtained in this way is confirmed by a detailed comparative analysis of the XAS spectra of the metal-protein complex at the Co K-edge. In particular, a fit to the EXAFS region of the spectrum allows positively identifying the frataxin acidic ridge as the most likely location of the metal-binding sites. Furthermore, we can explain the surprising feature emerging from a detailed analysis of the XANES region of the spectrum, showing that the longer 81-210 frataxin fragment has a smaller propensity for Co2+ binding than the shorter 90-210 one. This fact is explained by the peculiar role of the N-terminal disordered tail in modulating the protein ability to interact with the metal.

Characterisation of grids of point detectors in maximum skin dose measurement in fluoroscopically-guided interventional procedures.

PURPOSE: Point detectors are frequently used to measure patient's maximum skin dose (MSD) in fluoroscopically-guided interventional procedures (IP). However, their performance and ability to detect the actual MSD are rarely evaluated. The present study investigates the sampling uncertainty associated with the use of grids of point detectors to measure MSD in IP. METHOD: Chemoembolisation of the liver (CE), percutaneous coronary intervention (PCI) and neuroembolisation (NE) procedures were studied. Spatial dose distributions were measured with XR-RV3 Gafchromic(®) films for 176 procedures. These distributions were used to simulate measurements performed using grids of detectors such as thermoluminescence detectors, with detector spacing from 1.4 up to 10 cm. RESULTS: The sampling uncertainty was the highest in PCI and NE procedures. With 40 detectors covering the film area (36 cm × 44 cm), the maximum dose would be on average 86% and 63% of the MSD measured with Gafchromic(®) films in CE and PCI procedures, respectively. In NE procedures, with 27 detectors covering the film area (14 cm × 35 cm), the maximum dose measured would be on average 82% of the MSD obtained with the Gafchromic(®) films. CONCLUSION: Thermoluminescence detectors show good energy and dose response in clinical beam qualities. However the poor spatial resolution of such point-like dosimeters may far outweigh their good dosimetric properties. The uncertainty from the sampling procedure should be estimated when point detectors are used in IP because it may lead to strong underestimation of the MSD.

Measurement of maximum skin dose in interventional radiology and cardiology and challenges in the set-up of European alert thresholds.

To help operators acknowledge patient dose during interventional procedures, EURADOS WG-12 focused on measuring patient skin dose using XR-RV3 gafchromic films, thermoluminescent detector (TLD) pellets or 2D TL foils and on investigating possible correlation to the on-line dose indicators such as fluoroscopy time, Kerma-area product (KAP) and cumulative air Kerma at reference point (CK). The study aims at defining non-centre-specific European alert thresholds for skin dose in three interventional procedures: chemoembolization of the liver (CE), neuroembolization (NE) and percutaneous coronary interventions (PCI). Skin dose values of >3 Gy (ICRP threshold for skin injuries) were indeed measured in these procedures confirming the need for dose indicators that correlate with maximum skin dose (MSD). However, although MSD showed fairly good correlation with KAP and CK, several limitations were identified challenging the set-up of non-centre-specific European alert thresholds. This paper presents preliminary results of this wide European measurement campaign and focuses on the main challenges in the definition of European alert thresholds.

[THE RESULTS OF SCREENING OF DONATED BLOOD IN THE UKRAINE THE PRESENCE OF MARKERS HEMOTRANSMISYVNYH INFECTIONS IN 2010-2012 YEARS].

Prevalence level of HIV markers among blood and blood coMponent donors in European region of WHO increased from 8.3 to 10.3 positive cases per: 100,000 donations diring 2001-2006. In Ukraine from 2.1 to 112.3 positive cases per 100,000 donations in 2012. In 2010 and .2012 prevalence level of blood borne infections among Ukrainian donors was the following: HIV infection--112.3 positive cases per 100,000 donations; HCV--1498.1 cases and 1207.7 cases; HBsAg (hepatitis B surface antigen)--690.4 and 546.6 and antibodies to Tr. Pallidum--747 seropositive cases per 100,000 and 672.5 respectively. Specific weight of truly positive donations for HIV varied on test systems of different manufactures from 28.3% to 58.3% in 2010, from 12.2% to 61.8% in 2011 and from 20.7% to 63% in 2012. Significant fluctuation of results of confirmatory tests and high prevalence of HIV and HCV markers among Ukrainian donors displays a tendency to HIV prevalence which requires to define screening strategy of donated blood taking into consideration epidemiological studies and available state resources.

[The incidence of malignancies and surveillance of hematopoietic stem cells donors--the results of the Haemato-Oncology Department University Hospital in Plzen (Pilsen) and Czech National Marrow Donors Registry observation]. / Výskyt malignit a dispenzarizace dárcu krvetvorných bunek--výsledky sledování Hematologicko-onkologického oddelení FN Plzen a Ceského národního registru dárcu drene

BACKGROUNDS: Granulopoesis colony-stimulating factor filgrastim is used to mobilize peripheral stem cells but there are concerns regarding an elevated risk of haematological malignancies. We analyzed the incidence of malignancies and the system of haematopoietic stem cells donor surveillance. PATIENTS AND METHODS: prospective observation of sibling donors of the Haemato-Oncology Department University Hospital in Plzen (Pilsen) and of unrelated donors of the Czech National Marrow Donors Registry (CNMDR) in 2001-2010. RESULTS: No malignancy was observed in a group of 344 unrelated CNMDR donors, providing 753 person-years; one case of chronic lymphocytic leukaemia manifested 6 years after bone marrow donation, with leukaemia clone retrospectively detected by DNA analysis in blood samples taken prior to the marrow donation. Acute myeloid leukaemia, non-Hodgkin lymphoma, renal and colorectal carcinoma were observed in a group of 84 peripheral stem cells sibling donors, providing 337 person-years observation. The respective incidence of the two haematologic malignancies was 593 cases and the expected incidence rate was 143 per 100,000. The sibling (related) donors age was significantly higher: 48 (16-75) vs. 31 (20-42) years, (p<0.0001). Significantly more lost-to-follow-up donors were among the related donors (32% vs. 3%, p<0.0001), even though active surveillance system was implemented. CONCLUSION: The development of malignancies in hematopoietic stem cells donors can naturally be expected. Related (sibling) donors are at higher risk because of their generally older age, and higher susceptibility to haematological malignancies developed within the family. The contribution of filgrastim exposure needs to be further investigated. The follow-up cooperation with related (sibling) donors is limited.

[Molecular basis of Waldenström macroglobulinemia]. / Molekulární podstata Waldenströmovy makroglobulinemie.

Waldenström macroglobulinemia is a rare lymphoproliferative disease that is currently classified into lymphomas with incidence of 3 cases per million. This disease comprises about 1-2% of hematological malignancies and is characterized by infiltration of malignant B cells into the bone marrow and presence of monoclonal immunoglobulin IgM in serum. WM is still an incurable disease with median survival of 5 years. Molecular basis of this disease remains unclear even though deletion of 6q, trisomy of chromosomes 4 and 8, deletion of 13q and increased expression of IL-6 seem to be typical for this disease. The most important changes of microRNA are increased expression of miR-155 and decreased expression of miR-9*. This work aims to describe current knowledge about the molecular basis of this disease.

Organ and effective doses from verification techniques in image-guided radiotherapy.

The purpose of this work was an evaluation of organ doses and effective doses from three verification techniques in Image-Guided Radiotherapy: from kilovoltage (kV) cone beam computed tomography (CBCT) scans, from two orthogonal kV images and from two orthogonal megavoltage (MV) images for two different treatment sites: pelvis and head and neck (H&N). For comparison reasons, organ doses and effective doses from prostate and H&N radiotherapy were also evaluated. Measurements of organ doses were performed in a male anthropomorphic Rando phantom by means of thermoluminescent dosemeters. In this investigation, measured organ doses from one CBCT scan, from two MV images and from two kV images of pelvis represent typically 1-6, 1-10 and 0.05-1 %, respectively, of organ doses resulting from one fraction of prostate radiotherapy. The maximum effective doses from CBCT scans, kV images and MV images of pelvis are 5.6, 0.8 and 11.9 mSv, respectively.

[Penetrating thoracic and abdominal injuries: diagnostic and therapeutic approach]. / Penetrující poranení hrudníku a bricha: diagnostický a lécebný postup.

INTRODUCTION: Penetrating thoracic or abdominal or combined injuries are associated with high risk of life-threatening intraabdominal or intrathoracic organ injury. Most patients require acute surgery. When miniinvasive technique is available, thoracoscopic or laparoscopic intervention is indicated in hemodynamically stable patients to evaluate severity of the injury, as well as to treat the condition. AIM OF THE STUDY: Retrospective analysis of incidence, diagnostics and treatment of penetrating thoracic and abdominal injuries and combined thoracoabdominal injuries in a Trauma centre. PATIENTS, METHODS AND RESULTS: A total of 195 patients with penetrating thoracic, abdominal or combined injuries, who were hospitalized in the FNKV (Krilovské Vinohrady Faculty Hospital) Trauma centre in Prague from 1999 to 2010, were included in the study. The study group included 177 (91%) males. Out of the total, 102 patients (53%) suffered from penetrating abdominal injuries, 71 (36%) from thoracic injuries and 22 (11%) from combined, thoracoabdominal injuries. The majority of injuries were stab injuries (173, i.e. 89% of the patients). 22 subjects, the penetrating injury was caused by shot injuries. In stable patients, MDCT has been lately used to establish the diagnosis. In 171 subjects, acute thoracotomy or thoracotomy was indicated. Patients with combined injuries of the both cavities were indicated either for thoracotomy and laparotomy or thoracophrenolaparotomy. Videothoracoscopy or laparoskopy was conducted in 21 (11%) of the subjects. During the surgical revision, two subjects exited due to ireversible hemorrhagic shock, further 2 subjects died because of septic complications following shot abdominal injuries. CONCLUSION: Incidence of penetrating thoracic, abdominal or combined thoracoabdominal injuries is fairly rare in our country. Subjects with unstable hemodynamic conditions are indicated for acute thoracotomy or laparotomy. Miniinvasive procedures have diagnostic and therapeutic benefit in stable patients. Diagnostic thoracoscopy and laparocopy provides evidence of some injuries (diaphragm, alimentary tract). Therapeutically, miniinvasive methods may be used to manage the source of bleeding and for targeted drainage. Nonsurgical procedure is the method of choice in a selected group of hemodynamically stable patients with stab injuries, with monitoring of the patient's condition, including the use of x-ray imaging.

[Hemorrhagic complications of warfarin therapy]. / Hemoragické komplikace lécby warfarinem.

INTRODUCTION: Introduction of warfarin use in prevention and treatment of thromboembolic diseases resulted in lower rates of thromboembolic complications, however, on the other hand, it has been associated with increased incidence of hemorrhagic complications,which often require surgical management. AIM, MATERIAL, METHODS: The aim of the study was a retrospective analysis of hemorrhagic complications in 184 patients, hospitalized in the FNKV (Královské Vinohrady Faculty Hospital) Surgical Clinic during 2000-2008, following warfarin overdose. The following diagnostic or treatment methods were used: endoscopy of the upper or lower GIT in GIT hemorrhages and spiral CT when peritoneal bleeding was suspected. RESULTS: GIT bleeding, such as hematemesis, melena, enterorrhagy, was the commonest complication observed in 147 patients, ie. 79.9%. Upper GIT was identified as the source of bleeding in 76 subjects, i.e. 51.7%, lower GIT was the identified source in 26 subjects, ie. 17.7%, and the source remained unidentified in 45 patients, ie. in 30.6%. 10 patients suffered from soft tissue bleeding, m. rectus abdominis hematoma was detected in 7 subjects, hemoperitoneum and/or retrohemoperitoneum was identified in 8 subjects. Intestinal wall or its intestinal peritoneum was affected in 3 subjects and 3 patients suffered from liver or splenic intraparenchymal hematoma. Out of the total of 184 patients, 165 subjects were treated conservatively (89.7%), 19 subjects underwent surgery (10.3%), including 14 laparotomies for acute abdomen symptoms and 5 incisions with removal of hematomas. Overall lethality rate was 7/184, ie. 3.8%, 5 subjects undergoing conservative treatment and 2 subjects undergoing surgery exited. CONCLUSION: Uncontrolled warfarin administration may cause serious, even life- threatening complications. Therefore, patients undergoing warfarin therapy should be adequately informed about potential complications and regular INR monitoring is required.

Spinal extradural arachnoid cyst causing cord compression in a 15-year-old girl: a case report.

The authors describe the case of a fifteen-year-old girl with progressive paraparesis of the lower limbs that was caused by an intraspinal extradural dorsal arachnoid cyst at the level of Th 3-6. Diagnosis was established with MRI and MRI myelography. The latter revealed the CSF-like content of the cyst. The patient underwent laminotomy and en bloc resection of the cyst. Ligation of the pedicle of the cyst was done with laminoplasty. Quick and complete recovery was observed after surgery.

The structure of posterior subcapsular cataracts in the Royal College of Surgeons (RCS) rats.

The Royal College of Surgeons (RCS) rat is an animal model for human autosomal recessive retinitis pigmentosa. As the retinas of these animals degenerate from two to six weeks after birth, posterior subcapsular cataracts (PSCs) develop, presumably in response to toxic lipid peroxides formed by degenerating rod outer segments. Morphologically, these PSCs are thought to be characterized by a proliferation of dysplastic bladder-like fibers, or Wedl cells, in the meridional region of the lens, that subsequently migrate to, and aggregate at, the posterior pole as the PSC. This report presents the results of correlative scanning (SEM) and transmission (TEM) electron microscopic as well as light microscopic (LM) analysis of the ultrastructure of RCS PSCs. SEM analysis of two, four and six week old lenses (n=6-10 specimens per age group) demonstrated that the PSCs of RCS rats resulted from a growth malformation of the posterior fiber ends from four to six weeks. The PSC is composed of markedly enlarged and irregular posterior fiber ends aberrantly curved away from the polar axis toward the vitreous rather than overlapping and abutting to form suture branches within and between concentric growth shells. LM analysis revealed evidence of progressively more numerous, enlarged, and irregular, ovate cellular profiles at the posterior pole from four to six weeks. However, there was no evidence of Wedl cells either within the meridional row region or along a migratory path from the equator to the posterior pole at any age. TEM analysis confirmed that the size and abnormal shapes of cellular profiles were consistent with SEM analysis and that nuclei were never observed within the plaque. In addition, there was considerable variation in cytoplasmic densities between cells. Also, dense deposits were frequently noted between cells and beneath the capsule. The orientation of posterior fiber end profiles to the posterior capsule was 45, 70 and 90 degrees at respectively two, four and six weeks of age. These results show that RCS PSCs are a consequence of abnormal posterior fiber end growth culminating in a posterior opacity.

Production of a specific major histocompatibility complex class I-restricted epitope by ubiquitin-dependent degradation of modified ovalbumin in lymphocyte lysate.

Peptide epitopes presented through class I major histocompatability complex (MHC class I) on the cell surface, are generated by proteolytic processing of protein-antigens in the cytoplasm. The length and amino acid sequence determine whether a given peptide can fit into the peptide binding groove of class I heavy chain molecules and subsequently be presented to the immune system. The mode of action of the processing pathway is therefore of great interest. To study the processing mechanism of MHC class I-restricted intracellular antigens, we reconstituted the proteolytic processing of a model antigen in a cell-free system. Incubation of oxidized and urea-treated OVA in lymphocyte lysate resulted in partial degradation of the antigen. Degradation of the antigen depended on the presence of ATP. Addition of methylated ubiquitin abolished the reaction which was then restored by addition of an excess of native ubiquitin, indicating that the breakdown of the antigen in lymphocyte lysate is mediated by the ubiquitin proteolytic system. Upon incubation of modified OVA in lymphocyte lysate, a specific antigenic peptide was generated. The peptide was recognized by cytotoxic T lymphocytes directed against OVA-derived, H-2Kb-restricted peptide (SIINFEKL), and by a monoclonal antibody that recognizes cell-bound Kb-SIINFEKL complexes. Formation of the peptide epitope depended on the presence of ATP and ubiquitin. These results indicate that proteolytic processing of modified OVA is carried out by the ubiquitin-mediated degradation system. The experimental system described provides a tool to analyze the molecular mechanisms underlying the generation of specific, MHC class I-restricted peptide epitopes.

[First Hungarian experiences with positron emission tomography (PET) studies. Members of the PET working group]. / Elsö hazai tapasztalatok pozitron emissziós tomográfiás (PET) vizsgálatokkal. PET munkacsoport tagjai.

Diagnostic investigations commenced on the 28th of June 1994 in Hungary's and Central Europe's first PET Centre at the University Medical School of Debrecen. The Centre is equipped with a GE 4096 Plus whole body PET scanner. A metabolic tracer, 18F-deoxy-D-glucose (FDG), was used in the investigations. During the first 15 months 249 PET investigations were made in the Centre of which 242 were diagnostic and 7 normal subjects served as control for the patient studies with brain scans. The number of oncological indications (intra- and extracranial tumours, Hodgkin's lymphomas) was n = 105 (43.4% of the 242 diagnostic examinations), neurological investigations (without intracranial tumours) formed the dominant group (n = 117; 48.3%), whereas the number of cardiological indications was 20 (8.3%). The oncological studies included those of intracranial tumours (n = 76; 31.4%); thyroid tumours (n = 9; 3.7%); Hodgkin's lymphomas (n = 7; 2.9%) and other extracranial tumours (n = 13; 5.4%). The distribution of different neurological and psychiatric investigations was as follows: localization of focal epileptogen zone (n = 60; 24.8%); differential diagnosis of dementias (n = 30; 12.4%); exploration of cerebrovascular diseases (n = 10; 4.1%); and other neurological diseases (n = 17; 7.0%). The main objective of the cardiological PET investigations was the exploration of viable myocardium. The present paper overviews both the procedures (including administrative issues, as well) and the results of the first 249 FDG-PET investigations.

Correlation between central somatosensory conduction time, blood flow velocity, and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

In this retrospective study of 67 aneurysmal patients, the predictive role of central conduction time (CCT) on vasospasm occurrence evaluated by means of transcranial Doppler sonography (TCD) and the correlation of CCT to blood flow velocity measured simultaneously in postoperative course were studied. Data about the clinical state of patients at the time of admission (Hunt Hess scale), severity of subarachnoidal hemorrhage on initial CT scan (Fisher grade), timing of surgery (acute or delayed), outcome (Glasgow Outcome Scale), severity of vasospasm graded by highest mean blood flow velocity (BFV) during the entire clinical course and CCT values measured at admission (preoperatively), then postoperatively (one day after surgery) and simultaneously with later TCD investigations were collected from the files. Interhemispheric difference of CCT was also calculated. The results showed that CCT at admission was not predictive for vasospasm. CCT measured either at admission or on the first postoperative day did not differ significantly in the different grades of vasospasm. Similar results were obtained in the acute and in the late operated group of patients. The results also suggest that increased CCT and interhemispheric difference at the time of admission indicate a worse prognosis, but this can be related to higher surgical risk rather than to a higher incidence of late ischemic deterioration. Simultaneous CCT and TCD examinations demonstrated that coincident and statistically significant (p < 0.01) increase of actual CCT (6.7 msec) was found only in the severe grade of vasospasm (BFV 200 cm/s). The authors discuss the role of CCT and TCD monitoring in the management of aneurysmal subarachnoid hemorrhage.

10 years experience in performing Shouldice operation.

206 male patients were operated for primary direct and indirect inguinal hernia, or both, by Shouldice technique at general surgical departments of Madadeni Hospital, Newcastle, South Africa, Pásztó Hospital and Szolnok MAV Hospital, Hungary between 1986 and 1996. Mean age was 51 yrs +/- 15 yrs (17-91 yrs). The operations were performed by the original way of Shouldice described that type of hernia repair in 1945. 175 patients had spinal and 31 patients had local anesthesia with intravenous fluid and sedation respectively. Studies indicate that collagen metabolic dysfunction plays a major rule in the etiology of groin hernia. Until this is more clearly defined, surgeons will continue to repair groin hernias constitute 15% of operations in general surgery. In approach to groin hernia, the best view for examination of the inguinal region can be obtained by Shouldice technique to decide the proper surgical intervention to repair groin hernia. With low recurrence rate and rapid rehabilitation, author reports 2% of recurrence rate, the Shouldice operation highly recommended.

Craniospinal irradiation for acute lymphoblastic leukemia with central nervous system disease at diagnosis: a report from the Children's Cancer Group.

PURPOSE: This study attempted to determine if central nervous system (CNS) disease at diagnosis is a poor prognostic factor in children with acute lymphoblastic leukemia (ALL) and whether 6 Gy of spinal irradiation is an adequate dose for these patients. METHODS AND MATERIALS: Previously the Children's Cancer Group (CCG) treated patients with ALL and CNS disease at diagnosis with cranio (24 Gy)-spinal (12 Gy) irradiation, as well as systemic and intrathecal chemotherapy. In a series of CCG trials completed in 1989 the spinal dose was empirically reduced to 6 Gy for patients receiving systemic chemotherapy with an intensive consolidation phase to limit hematopoietic toxicity. The spinal dose was left at 12 Gy for patients treated with a less intensive consolidation phase. RESULTS: With a median follow-up for surviving patients of 74 months, the 5-year event-free survival for 53 patients with CNS disease at diagnosis was 69 +/- 13% (+/- 2 standard deviations), similar to the value obtained for 3364 patients without CNS disease, 67 +/- 2%. Corresponding values for 5-year survival were 77 +/- 12% and 80 +/- 1%, and for freedom from isolated first CNS relapse, were 90 +/- 9% and 94 +/- 1%. Event-free survival, survival, and freedom from isolated first CNS relapse in the 6-Gy group were as good as in the 12-Gy group. CONCLUSION: CNS disease at diagnosis is not a poor prognostic factor for children with ALL who are treated with intensive systemic chemotherapy, craniospinal irradiation, and intrathecal chemotherapy. Six Gy is an adequate dose of spinal irradiation for these patients.

Regiospecific intestinal absorption of the HIV protease inhibitor L-735,524 in beagle dogs.

PURPOSE: To evaluate regional intestinal absorption and the feasibility of sustained release dosage form development for an HIV protease inhibitor, L-735,524, METHODS: L-735,524 free base or sulfate salt was administered orally as suspension, solution or in solid dosage forms to fasted or fed Beagle dogs. Delayed-release dosage forms with "slow" or "fast" in vitro dissolution rates were evaluated in vivo to assess plasma concentration profiles. In addition, drug was administered directly into the jejunum or colon of animals, and drug concentrations determined in portal circulation to characterize absorption from these sites. RESULTS: L-735,524 sulfate was well absorbed orally form a solution or capsule formulation if fasted animals' stomachs were preacidified with citric acid solution. A free base suspension, delivered in divided doses to fed animals, was also well absorbed. Prototype extended release dosage forms of L-735,524 produced a reduction in peak plasma levels but failed to prolong absorption and extend plasma concentrations compared to an immediate release capsule. Administration of L-735,524 sulfate solution (pH < 3) as bolus solution or by infusion into the jejunum resulted in rapid but incomplete absorption compared to oral gavage. The free base suspension (pH 6.5) delivered into jejunal or colonic regions did not produce measurable systemic plasma concentrations. CONCLUSIONS: Extended release formulations did not prolong absorption of L-735,524 in dogs. Optimal L-735,524 absorption was dependent on solubility in an acidic environment in the duodenum.

Neuropsychological effects of cranial irradiation in young children with acute lymphoblastic leukemia 9 months after diagnosis. The Children's Cancer Group.

STUDY OBJECTIVE: To determine the effects of cranial irradiation on neuropsychological test performance evident 9 months after diagnosis. DESIGN: A companion study to a randomized clinical trial (CCG-105). SETTING: Institutions participating in Childrens Cancer Group cooperative treatment trials. PATIENTS: Seventy-four children aged 3.0 to 6.5 years with average-risk acute lymphoblastic leukemia. Children with central nervous system leukemia at the time of diagnosis, preexisting mental retardation, or Down's syndrome or for whom English was not the primary language were not eligible for study. INTERVENTIONS: Children were randomized to receive treatment with one of four systemic chemotherapy regimens and either intrathecal methotrexate sodium during induction and consolidation plus 18 Gy of cranial irradiation or intrathecal methotrexate during induction, consolidation, and maintenance as central nervous system prophylaxis. MEASUREMENT AND RESULTS: The groups were comparable with regard to chronologic age, sex, and family socioeconomic status. Children who received cranial irradiation plus intrathecal methotrexate scored significantly lower on the McCarthy Motor Scale (P < .05) and the Token Test (P < .05) than children who received intrathecal methotrexate alone. The groups did not differ significantly on the McCarthy General Cognitive Index, Developmental Test of Visual Motor Integration, or Peabody Picture Vocabulary Test-Revised. CONCLUSIONS: Findings suggest that the combined effects of cranial irradiation and intrathecal methotrexate therapy on neuropsychological performance may be evident in young children as early as 9 months after diagnosis. Follow-up assessment of these children will reveal whether these effects remain constant, intensify, or resolve.