scholarly journals An In Vivo Confocal Microscopic Study of Corneal Nerve Morphology in Unilateral Keratoconus

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Natasha Kishore Pahuja ◽  
Rohit Shetty ◽  
Rudy M. M. A. Nuijts ◽  
Aarti Agrawal ◽  
Arkasubhra Ghosh ◽  
...  
Keyword(s):  
Nerve Fiber ◽  
Nerve Branch ◽  
Intergroup Comparison ◽  
Corneal Nerve ◽  
Group 3 ◽  
Group 2 ◽  
Branch Density ◽  
Corneal Nerve Morphology ◽  
Group 1

Purpose.To study the corneal nerve morphology and its importance in unilateral keratoconus.Materials and Methods.In this prospective cross-sectional study, 33 eyes of 33 patients with keratoconus in one eye (Group 3) were compared with the other normal eye of the same patients (Group 2) and 30 eyes of healthy patients (Group 1). All patients underwent detailed ophthalmic examination followed by topography with Pentacam HR and in vivo confocal microscopy (IVCM). Five images obtained with IVCM were analyzed using an automated CCmetrics software version 1.0 for changes in subbasal plexus of nerves.Results.Intergroup comparison showed statistically significant reduction in corneal nerve fiber density (CNFD) and length (CNFL) in Group 3 as compared to Group 1 (p<0.001andp=0.001, resp.) and Group 2 (p=0.01andp=0.02, resp.). Though corneal nerve fiber length, diameter, area, width, corneal nerve branch density, and corneal total branch density were found to be higher in decentered cones, only the corneal nerve branch density (CNBD) was found to be statistically significant (p<0.01) as compared to centered cones.Conclusion.Quantitative changes in the corneal nerve morphology can be used as an imaging marker for the early diagnosis of keratoconus before the onset of refractive or topography changes.

scholarly journals Comparing the results of manual and automated quantitative corneal neuroanalysing modules for beginners

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Po-Ying Wu ◽  
Jo-Hsuan Wu ◽  
Yi-Ting Hsieh ◽  
Lin Chih-Chieh Chen ◽  
Ting Cheng ◽  
...  
Keyword(s):  
Nerve Fiber ◽  
Correlation Coefficient ◽  
Intraclass Correlation ◽  
Fiber Density ◽  
Nerve Branch ◽  
Observer Reliability ◽  
Automated Method ◽  
Corneal Nerve ◽  
Branch Density

AbstractThis study aimed to evaluate the reliability of in vivo confocal microscopic neuroanalysis by beginners using manual and automated modules. Images of sub-basal corneal nerve plexus (SCNP) from 108 images of 18 healthy participants were analyzed by 7 beginner observers using manual (CCMetrics, [CCM]) and automated (ACCMetrics, [ACCM]) module. SCNP parameters analyzed included corneal nerve fiber density (NFD), corneal nerve branch density (NBD), corneal nerve fiber length (NFL), and tortuosity coefficient (TC). The intra-observer repeatability, inter-observer reliability, inter-module agreement, and left–right eye symmetry level of SCNP parameters were examined. All observers showed good intra-observer repeatability using CCM (intraclass correlation coefficient [ICC] > 0.60 for all), except when measuring TC. Two observers demonstrated especially excellent repeatability in analyzing NFD, NBD, and NFL using manual mode, indicating the quality of interpretation may still be observer-dependent. Among all SCNP parameters, NFL had the best inter-observer reliability (Spearman’s rank-sum correlation coefficient [SpCC] and ICC > 0.85 for the 3 original observers) and left–right symmetry level (SpCC and ICC > 0.60). In the additional analysis of inter-observer reliability using results by all 7 observers, only NFL showed good inter-observer reliability (ICC = 0.79). Compared with CCM measurements, values of ACCM measurements were significantly lower, implying a poor inter-module agreement. Our result suggested that performance of quantitative corneal neuroanalysis by beginners maybe acceptable, with NFL being the most reliable parameter, and automated method cannot fully replace manual work.

In-vivo evaluation of the effect of cyanoacrylate on prosthetic vascular graft infection – does cyanoacrylate increase the severity of infection?

VASA ◽  
2020 ◽  
Vol 49 (4) ◽  
pp. 281-284
Author(s):  
Atıf Yolgosteren ◽  
Gencehan Kumtepe ◽  
Melda Payaslioglu ◽  
Cuneyt Ozakin
Keyword(s):  
Vascular Graft ◽  
Graft Infection ◽  
Vascular Graft Infection ◽  
Group 4 ◽  
Significant Difference ◽  
Group 3 ◽  
Group 2 ◽  
Prosthetic Vascular Graft Infection ◽  
Group 1

Summary. Background: Prosthetic vascular graft infection (PVGI) is a complication with high mortality. Cyanoacrylate (CA) is an adhesive which has been used in a number of surgical procedures. In this in-vivo study, we aimed to evaluate the relationship between PVGI and CA. Materials and methods: Thirty-two rats were equally divided into four groups. Pouch was formed on back of rats until deep fascia. In group 1, vascular graft with polyethyleneterephthalate (PET) was placed into pouch. In group 2, MRSA strain with a density of 1 ml 0.5 MacFarland was injected into pouch. In group 3, 1 cm 2 vascular graft with PET piece was placed into pouch and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. In group 4, 1 cm 2 vascular graft with PET piece impregnated with N-butyl cyanoacrylate-based adhesive was placed and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. All rats were scarified in 96th hour, culture samples were taken where intervention was performed and were evaluated microbiologically. Bacteria reproducing in each group were numerically evaluated based on colony-forming unit (CFU/ml) and compared by taking their average. Results: MRSA reproduction of 0 CFU/ml in group 1, of 1410 CFU/ml in group 2, of 180 200 CFU/ml in group 3 and of 625 300 CFU/ml in group 4 was present. A statistically significant difference was present between group 1 and group 4 (p < 0.01), between group 2 and group 4 (p < 0.01), between group 3 and group 4 (p < 0.05). In terms of reproduction, no statistically significant difference was found in group 1, group 2, group 3 in themselves. Conclusions: We observed that the rate of infection increased in the cyanoacyrylate group where cyanoacrylate was used. We think that surgeon should be more careful in using CA in vascular surgery.

A TRIAL OF SUBCUTANEOUS VERSUS INTRAVENOUS ADMINISTRATION OF LOW MOLECULAR WEIGHT (LMW) HEPARIN AND UNFRACTIONATED (UF) HEPARIN IN THE TREATMENT OF ESTABLISHED DEEP VENOUS THROMBOSIS (DVT)

1987 ◽  
Author(s):  
C J Parker ◽  
D E Huber ◽  
A R Hedges ◽  
V V Kakkar
Keyword(s):  
Low Molecular Weight ◽  
Heparin Group ◽  
Expert Radiologist ◽  
Intravenous Heparin ◽  
Antithrombotic Effects ◽  
Group 3 ◽  
Group 2 ◽  
Efficacy Of Treatment ◽  
Group 1

In a randomized clinical trial of 100 patients, the in vivo antithrombotic effects of a subcutaneously administered LMW heparin fraction (CY216) used in the treatment of established DVT, was compared with UF heparin administered by either intravenous or subcutaneous routes.Venograms were used to make the initial diagnosis, and efficacy of treatment was assessed by a repeat venogram done on day 6. Comparison of the venograms were done blind by an expert radiologist.Patients were randomized to one of three groups: Group 1 received subcutaneous CY216; Group 2 received subcutaneous UF heparin: Group 3 received continuous intravenous UF heparin. Random patients from each group had detailed haematological tests consisting of twicedaily KCCT and anti-Xa levels. Extension of thrombus occurred in significantly morepatients receiving intravenous heparin than subcutaneous heparin (p-0.02).There was no difference between the two subcutaneousgroups. There were no haematological complications.We conclude that subcutaneous administratiyon of heparin is the treatment of choice in the treatment of DVT.

Micropuncture study of the effect of ANP on the papillary collecting duct in the rat

1988 ◽  
Vol 254 (4) ◽  
pp. F477-F483 ◽  
Author(s):  
A. van de Stolpe ◽  
R. L. Jamison
Keyword(s):  
Collecting Duct ◽  
Sodium Concentration ◽  
Sodium Reabsorption ◽  
Micropuncture Study ◽  
Papillary Collecting Duct ◽  
Group 3 ◽  
Group 2 ◽  
Tubule Fluid ◽  
Group 1

Micropuncture collections were obtained from the terminal collecting duct (CD) at base and tip of the renal papilla of the rat. Group 1 was studied before and during infusion with atrial natriuretic peptide (ANP), group 2 was administered the vehicle only, and group 3 received acetazolamide to increase sodium delivery to the base to a similar extent as after ANP. ANP caused a decrease in blood pressure, a slight increase in GFR, natriuresis, and diuresis. Sodium delivery to the collecting duct at the base of the papilla increased. Between base and tip, sodium reabsorption was inhibited. Tubule fluid sodium concentration (TFNa) was increased at the base and remained high at the tip; in contrast TFNa fell between base and tip in control and acetazolamide groups. After acetazolamide, sodium reabsorption in the terminal CD was not inhibited. These results demonstrate that in vivo ANP 1) increases the delivery of sodium to the terminal CD and 2) inhibits sodium reabsorption in the terminal CD. The findings for chloride were similar to those for sodium. ANP also increased delivery of H2O, K, Ca, and Mg to the CD at the papillary base but did not significantly affect their transport by the terminal CD.

scholarly journals Prophylaxis protocols and their impact on bracket friction force

2019 ◽  
Vol 89 (6) ◽  
pp. 883-888
Author(s):  
Sérgio Elias Neves Cury ◽  
Silvio Augusto Bellini-Pereira ◽  
Aron Aliaga-Del Castillo ◽  
Sérgio Schneider ◽  
Arnaldo Pinzan ◽  
...  
Keyword(s):  
Sodium Bicarbonate ◽  
Qualitative Analysis ◽  
Friction Force ◽  
Friction Forces ◽  
Debris Accumulation ◽  
Intergroup Comparison ◽  
Group 3 ◽  
Group 2 ◽  
Sliding Mechanics

ABSTRACT Objective: To evaluate the effect of two different prophylaxis protocols on the friction force in sliding mechanics during in vivo leveling and alignment. Materials and Methods: The sample comprised 48 hemi-arches divided into three groups according to the prophylactic protocol adopted. Group 1 consisted of patients undergoing prophylaxis with sodium bicarbonate, group 2 consisted of patients submitted to prophylaxis with glycine, and group 3 consisted of patients without prophylaxis, as a control. All patients received hygiene instructions and, with the exception of group 3, prophylaxis was performed monthly. After 10 months, the brackets were removed from the oral cavity and submitted to friction force tests and qualitative analysis by scanning electron microscopy. Analysis of variance followed by Tukey tests was performed for intergroup comparison regarding the friction force. Results: The experimental groups presented significantly smaller friction forces than the group without prophylaxis. Accordingly, qualitative analysis showed greater debris accumulation in the group without the prophylactic procedures. Conclusions: Prophylactic blasting with sodium bicarbonate or glycine can significantly prevent an increase of the friction force during sliding mechanics.

scholarly journals In Vivo Confocal Microscopy of the Corneal Sub-Basal Nerve plexus in Medically Controlled Glaucoma

2022 ◽  
pp. 1-8
Author(s):  
Luca Agnifili ◽  
Lorenza Brescia ◽  
Edoardo Villani ◽  
Giada D'Onofrio ◽  
Michele Figus ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Nerve Fibers ◽  
Nerve Plexus ◽  
Ocular Surface Disease Index ◽  
Corneal Nerves ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

The present study investigated the corneal sub-basal nerve plexus (SNP) modifications in glaucoma. Ninety-five glaucomatous patients were enrolled and divided into Group 1 and 2, preserved and preservative-free mono-therapy (30 and 28 patients), and Group 3, multi-therapy (37). Thirty patients with dry eye disease (DED) and 32 healthy subjects (HC) served as controls. In vivo confocal microscopy evaluated the nerve fibers density (CNFD), length (CNFL), thickness (CNFT), branching density (CNBD), and dendritic cell density (DCD). CNFD, CNFL, and CNBD were reduced in Group 3 and DED compared to HC (p < 0.05). CNFL was reduced in Group 3 compared to Group 2 (p < 0.05), and in Group 1 compared to HC (p < 0.001). CNFD, CNBD, and CNFT did not differ between glaucomatous groups. DCD was higher in Group 3 and DED compared to HC and Group 2 (p < 0.01). Group 3 showed worse ocular surface disease index (OSDI) scores compared to Group 1, 2, and HC (p < 0.05). CNFL and DCD correlated with OSDI score in Group 3 (r = −0.658, p < 0.001; r = 0.699, p = 0.002). Medical therapy for glaucoma harms the corneal nerves, especially in multi-therapy regimens. Given the relations with the OSDI score, SNP changes seem features of glaucoma therapy-related OSD and negatively affects the patient's quality of life.

scholarly journals Testing the Medina embolization device in experimental aneurysms

2019 ◽  
Vol 131 (5) ◽  
pp. 1485-1493 ◽  
Author(s):  
Robert Fahed ◽  
Tim E. Darsaut ◽  
Igor Salazkin ◽  
Guylaine Gevry ◽  
Jean Raymond
Keyword(s):  
Flow Diverter ◽  
Group 3 ◽  
Group 2 ◽  
Aneurysmal Neck ◽  
Near Occlusion ◽  
Platinum Coils ◽  
Group 1

OBJECTIVEThe Medina embolization device (MED) is a novel, braided self-expanding endovascular device designed to occlude aneurysms by constructing an in situ intrasaccular flow diverter. Although a single device can be positioned at the neck of simple spherical in vitro aneurysms, the best way to occlude more complex in vivo aneurysms (using multiple MEDs or a combination of MEDs and platinum coils) is currently unknown.METHODSFifty-two aneurysms of 3 different types were created in 31 canines, yielding 48 patent aneurysms. Treatments were randomly allocated by drawing lots: group 1, MEDs alone (n = 16); group 2, MEDs plus standard platinum coils (n = 16); and group 3, control aneurysms treated with coils alone (n = 16). Angiographic results were scored and compared immediately following treatment completion and at 3 months. Specimens were photographed and the extent of neointimal closure of the aneurysmal neck scored, followed by histopathological analyses.RESULTSAngiographic scores of 0 or 1 (occlusion or near occlusion) were initially obtained in 2 of 16 (12.5%, 95% CI 1.6%–38.3%) group 1 (MEDs alone), 3 of 16 (18.7%, 95% CI 4%–45.6%) group 2 (MEDs plus coils), and 10 of 16 (62.5%, 95% CI 35.4%–84.8%) group 3 (coils alone) aneurysms (p = 0.005). At 3 months, scores of 0 or 1 were found in 11 of 16 (68.7%, 95% CI 41.3%–89.0%) group 1, 9 of 16 (56.2%, 95% CI 29.9%–80.2%) group 2, and 8 of 16 (50%, 95% CI 24.7%–75.3%) group 3 aneurysms (p = 0.82). Neointimal scores were similar for the 3 treated groups (p = 0.66).CONCLUSIONEndovascular treatment of experimental aneurysms with MEDs or MEDs and coils showed angiographic occlusion and neointimal scores at 3 months that were similar to those achieved with standard platinum coiling.

97 PRELIMINARY DESCRIPTIVE STUDY OF EQUINE PLACENTA GENERATED AFTER TRANSFER OF IN VIVO- AND IN VITRO-PRODUCED EMBRYOS

2017 ◽  
Vol 29 (1) ◽  
pp. 156 ◽  
Author(s):  
A. Lanci ◽  
J. Mariella ◽  
B. Merlo ◽  
C. Castagnetti ◽  
E. Iacono
Keyword(s):  
Embryo Transfer ◽  
Intracytoplasmic Sperm Injection ◽  
Reproductive Technologies ◽  
Control Group ◽  
Placental Development ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Placental changes associated with artificial reproductive technologies have been described in several species, but little information is available in horses. Joy et al. (2012) reported that human placentas from intracytoplasmic sperm injection derived embryos were heavier and thicker than those produced after natural conception. Despite the most growing interest and efficiency of artificial reproductive technologies in equine species, only recently, Pozor et al. (2016) described placental abnormalities in pregnancies generated by somatic cell NT, but there are no studies on equine placenta generated by intracytoplasmic sperm injection and traditional embryo transfer. In the present preliminary study, macroscopic differences of placentas generated after transfer of in vitro- or in vivo-produced embryos were registered. Twelve Standardbred recipient mares with pregnancy generated after transfer of in vivo-derived (Group 1) and in vitro-derived (Group 2) embryos were enrolled; 10 Standardbred mares with pregnancy derived by traditional AI were included as control (Group 3). All pregnancies were physiological, and newborn foals were healthy. Mare age, parity, length of pregnancy, gross evaluation and weight of placenta, total length of umbilical cord (UC), length of UC, number of UC coils, foal sex, and weight at birth were registered. Collected data are listed in Table 1 and are expressed as mean ± standard deviation. Differences between groups were evaluated by 1-way ANOVA, and the difference in proportion of overweight placentas was evaluated with the Fisher test. The gross evaluation of placenta revealed 8/12 placentas (2/4 Group 1; 6/8 Group 2) were heavier than 11% (Madigan, 1997) due to oedema of the chorioallantois. No overweight placentas were registered in Group 3. In Group 1, 1/4 placentas had villous hypoplasia, and in Group 2, 1/8 placentas had cystic pouches on the UC. There were no significant differences among groups. However, the proportion of overweight placentas between Group 2 (6/8) and Group 3 (0/10) approached significance (P = 0.06). Although preliminary, the results of the present study suggest that production of equine embryos in vitro may lead to alterations in placental development. Several studies in cattle and sheep have suggested that alterations in the placentas of pregnancies derived from in vitro-produced embryos are related to effects of culture on epigenetic regulation. Less is known in the horse about the effects of in vitro embryo production on placental development; thus, further research in this area is necessary. Table 1. Characteristics of full-term placentas derived from AI or embryo transfer with in vivo- and in vitro-produced embryos

Higher Percentage of CD34+CD38− Cells Detected by Multiparameter Flow Cytometry From Leukapheresis Products Predict Unsustained Complete Remission in AML

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1485-1485
Author(s):  
Adriana Plesa ◽  
Mohamed Elhamri ◽  
Gilles Clapisson ◽  
Eve Mattei ◽  
Sophie Gazzo ◽  
...  
Keyword(s):  
Leukemic Cells ◽  
Prognostic Impact ◽  
Entire Cohort ◽  
Cd34 Cells ◽  
Group A ◽  
Autologous Pbsct ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Abstract 1485 Aim: Myeloablative chemotherapy followed by autologous PBSCT remains one treatment strategy in adult AML patients. Relapse has been shown higher for those who received the highest CD34+ PB doses. Although highly active against the leukemic bulk, intensive chemotherapy often spare the hardier leukemia stem cells (LSCs) responsible for relapse. Detection of MRD in harvest products may reflect inadequate in vivo purging at least in part responsible for relapses. Although recent data have challenged the CD34+CD38− phenotype of LSCs, this cell population remains generally considered enriched for LSCs. In this setting, MRD remaining during CR should be relatively enriched in CD34+CD38− leukemic cells and their persistence should correlate with disease recurrence. Methods: CD34+ cells were harvested after CR achievement in 123 AML patients [median age: 53 y (25–72)] treated by induction chemotherapy in our Institution between 10/1994 and 04/2003. Patients were included in different clinical trials planning autologous SC harvest in CR and autologous SCT in absence of donor or allogeneic SCT indication. Seventy-one of them received effectively autologous PBSCT. Harvests performed in 15 normal donors were used as controls. CD34/CD38 cell profile was analyzed in harvests in one single tube by multicolor flow cytometry using multiple MoAbs. The gating strategy was based on CD45low/SSC and CD34+CD45low cell populations from total FSC/SSC viable cells. Three populations of CD34+ were distinguished: CD34+CD38–; CD34+CD38low; and CD34+CD38+. Results: Patients from the entire cohort with higher percentage of CD34+ cells (cut-off level: 1%) in PBSC products were associated with shorter EFS [median: 5.6 months (3-y EFS: 13%) vs 13.6 (37%); p=0.0005] and OS [median: 10 months (3-y OS: 19%) vs 23.4 (47%); p=0.004]. This was also the case when analyzing only patients who received autologous SCT: [median EFS: 5 months (3-y EFS: 13%) vs 22.2 (48%); p=0.0006, and median OS: 9.1 months (3-y OS: 21%) vs 43.3 (57%); p=0.001]. Among CD34+ populations, only CD34+CD38– had a prognostic impact on EFS and OS. At a cut-off level of 0.9%, median EFS was 8.2 months (3-y EFS: 29%) for those with higher percentage vs 91.9 (62%) for those with lower percentage and median OS was 14.2 months (3-y OS: 36%) vs 95.4 (69%) respectively for the entire cohort. These results were confirmed in patients undergoing autologous SCT: median EFS was 7.3 months (3-y EFS: 31%) vs 91.1 (70%) (p= 0.05), and median OS was 14.4 months (3-y OS: 39%) vs 94.6 (80%). CD34+CD38low and CD34+CD38+ populations did not show any prognostic impact. Harvests from AML patients were divided into 3 groups: Group A: 51 patients with CR duration <1 y; Group B: 22 patients with CR duration >1 y; and Group C: 50 patients without relapse. Harvests from 15 normal donors (Group D) were used as controls. Significant differences were only observed when comparing Group A and Group D for total CD34+ cells (mean ± SEM 2.5 ± 0.5 vs 1.2 ± 0.3; p < 0.05) and CD34+CD38– (4.5 ± 0.7 vs 2.3 ± 0.5; p < 0.05). To confirm the prognostic value of CD34+CD38–, 19 patients (Group 1) with evidence of leukemic contamination in harvests (abnormal cytogenetics at presentation found in aphereses) were compared with 22 patients (Group 2) without evidence of contamination (abnormal cytogenetics at presentation not found in aphereses). Median EFS was 10.1 months (3-year EFS: 45%) in Group 2 vs 6.3 (13%) in Group 1 (p=0.01), and median OS was 36.6 months (3-year OS: 55%) vs 10.8 (23%), respectively (p=0.03). Harvests from 15 normal donors (Group 3) served as controls. Significant differences were noted in harvest products regarding CD34+CD38– between Group 1 and Group 3 (mean ± SEM 6.0 ± 1.5 vs 2.3 ± 0.5; p = 0.04) and Group 1 and Group 2 (6.0 ± 1.5 vs 2.4 ± 0.5; p = 0.03), while there were no differences between Group 2 and controls. There were no significant differences between groups regarding CD34+CD38low and CD34+CD38+. We also measured MFI of CD13, CD33, CD123, CD117 in CD34+ subpopulations. Phenotypes were compared among the different groups. Conclusions: Higher proportions of CD34+CD38− in apheresis products appear to reflect inadequate in vivo purging and distinguish samples as enriched in ‘leukemic cells’ from those with lower CD34+CD38− as largely constituted of ‘normal cells’. This could serve as detection of MRD and help to identify samples associated with high-risk of relapse after autologous SCT. Disclosures: No relevant conflicts of interest to declare.

Systemic effect of intrathecal methotrexate during the initial phase of treatment of childhood acute lymphoblastic leukemia. The European Organization for Research and Treatment of Cancer Children's Leukemia Cooperative Group.

1997 ◽  
Vol 15 (5) ◽  
pp. 1824-1830 ◽  
Author(s):  
A Thyss ◽  
S Suciu ◽  
Y Bertrand ◽  
F Mazingue ◽  
A Robert ◽  
...  
Keyword(s):  
Lymphoblastic Leukemia ◽  
Systemic Effect ◽  
Cooperative Group ◽  
European Organization ◽  
Blast Count ◽  
Group 3 ◽  
Group 2 ◽  
B Lineage ◽  
Group 1

PURPOSE The in vivo response to prephase corticosteroid therapy for 1 week has been described as a major prognostic factor in childhood acute lymphoblastic leukemia (ALL). Patients with less than 1,000 blasts/microL at day 8 are considered responders and have a better prognosis. This prephase therapy is usually considered as an evaluation of glucocorticoid sensitivity. In fact, it also includes one intrathecal (IT) injection of methotrexate (MTX). In this study, we try to clarify the influence of this injection of IT MTX on the response to the prephase therapy. PATIENTS AND METHODS This retrospective study analyzed the response to prephase therapy in 1,044 children with ALL entered onto the European Organization for Research and Treatment of Cancer (EORTC) trial 58881 of the Children's Leukemia Cooperative Group (CLCG). Analysis was restricted to 732 cases with an initial blast count greater than 1,000/microL. The following variables were tested to analyze response to prephase therapy: age, sex, evaluated risk factor (RF), blast count on day 0, actual dose of prednisolone administered, immunophenotype (T v non-T), and day of IT MTX. For statistical analysis, the variable day of IT MTX (D) was stratified into three groups: group 1 if D less than 2, group 2 if D > or = 2 but < or = 6, and group 3 if D greater than 6. RESULTS All variables tested had a significant influence on response to the prephase therapy. This was especially true for IT MTX: 90.4% responders in group 1, 76.9% in group 2, and 70% in group 3 (P < .001). Immunophenotype was also a major predictor of response to the prephase: 88% responders in B-lineage ALL versus 56.2% in T-lineage ALL. IT MTX had a significant influence in B-lineage ALL (96% responders in group 1, 90% in group 2, and 79% in group 3; P < .001), whereas the influence could not be detected in T-lineage ALL. CONCLUSION These results clearly demonstrate a therapeutic systemic effect of low doses of IT MTX in childhood ALL, and response to prephase therapy should not be considered as an in vivo test for cortico-sensitivity only. Earlier use of IT MTX leads to a higher percentage of responders.

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