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Objective Frontonasal dysplasia is a rare developmental defect of the midface, and little is known about the dental involvement in individuals with this condition. This study investigated tooth abnormalities and occlusal disorders in individuals with frontonasal dysplasia.Design Cross-sectional.Setting Hospital for Rehabilitation of Craniofacial Anomalies, University of São Paulo, Bauru, Brazil.Interventions Clinical oral examination, analysis of patient records, and panoramic radiographs.Participants A total of 20 individuals with frontonasal dysplasia aged 7 to 17 years.Main Outcome Measures Prevalence of the several tooth abnormalities and occlusal disorders analyzed.Results A total of 19 individuals presented at least one tooth abnormality, with highly variable findings. In radiographs, 20% of individuals (all presenting oral clefts) presented agenesis of lateral incisors and second premolars. No supernumerary teeth were observed; 65% of individuals exhibited occlusal alterations, especially anterior open bite in the two individuals with median cleft lip.Conclusions Variable clinical and radiographic alterations were observed, probably due to the large variety of phenotypic characteristics. No specific dental alteration could be related with frontonasal dysplasia.

Recent research suggests that some people with aphasia preserve some ability to learn novel words and to retain them in the long-term. However, this novel word learning ability has been studied only in the context of single word-picture pairings. We examined the ability of people with chronic aphasia to learn novel words using a paradigm that presents new word forms together with a limited set of different possible visual referents and requires the identification of the correct word-object associations on the basis of online feedback. We also studied the relationship between word learning ability and aphasia severity, word processing abilities, and verbal short-term memory (STM). We further examined the influence of gross lesion location on new word learning. The word learning task was first validated with a group of forty-five young adults. Fourteen participants with chronic aphasia were administered the task and underwent tests of immediate and long-term recognition memory at 1 week. Their performance was compared to that of a group of fourteen matched controls using growth curve analysis. The learning curve and recognition performance of the aphasia group was significantly below the matched control group, although above-chance recognition performance and case-by-case analyses indicated that some participants with aphasia had learned the correct word-referent mappings. Verbal STM but not word processing abilities predicted word learning ability after controlling for aphasia severity. Importantly, participants with lesions in the left frontal cortex performed significantly worse than participants with lesions that spared the left frontal region both during word learning and on the recognition tests. Our findings indicate that some people with aphasia can preserve the ability to learn a small novel lexicon in an ambiguous word-referent context. This learning and recognition memory ability was associated with verbal STM capacity, aphasia severity and the integrity of the left inferior frontal region.

Background:Singlelaboratory experience showed that flow cytometric FCM assessment of minimal residual disease MRD in acute lymphoblastic leukemia ALL is feasible in most patients and gives independent prognostic information. It is, however, not known whether FCM analysis can reliably be standardized for multicentric application.Methods:An extensive standardization program was installed in four collaborating laboratories, which study FCMMRD in children treated with the AIEOPBFMALL 2000 protocol. This included methodological alignment, continuous quality monitoring, as well as personnel education by exchange and performance feedback.Results:Blinded interlaboratory tests of listmode data interpretation concordance n 202 blood and bone marrow samples from followup during induction of 31 randomly selected patients of a total series of n 395 showed a very high degree of interrater agreement among the four centers despite differences in cytometers and software usage intraclass correlation coefficient ICC 0.979 based on n 800 single values. Lower concordance was reached with amounts of MRD below 0.1. Comparing data from sample exchange experiments n 42 samples; ICC 0.98 and from independent patient cohorts from the four centers regarding positive samples per timepoint of followup as well as risk estimates concordance was also good.Conclusion:MRDevaluation by FCM in ALL can be standardized for reliable multicentric assessment in large trials. © 2008 Clinical Cytometry Society.

Although it is the treatment of choice in the management of idiopathic Parkinson’s disease, l-DOPA (LD) shows a decline in its efficacy after years of prolonged use, with the appearance of severe motor disturbances. These complications have been interpreted on pharmacokinetic and pharmacodynamic grounds. The main pharmacokinetic reason is considered to be the decreased capacity in LD activation to dopamine along with reduction of its storage ability in the nigrostriatal terminals, as a result of disease progression. At this stage the LD action in the extrapyramidal system is thought to be closely dependent on its synaptic cleft concentrations, being directly related to those in the systemic circulation and to the events possibly perturbing them. Therapeutic drug monitoring might be useful to explain these modifications in relation to the clinical effect and even to possible problems in transport competition and so to define the LD dosage regimen. Recently LD threshold concentrations have been suggested by means of sophisticated pharmacokinetic–pharmacodynamic approaches. Unfortunately they do not correspond to real therapeutic ranges but to levels in a hypothetical effect compartment in no steady-state conditions, due to remarkable LD fluctuations. However they are considered helpful to the functional state interpretation of the nigrostriatal system.

The purpose of this study was to compare the effect of direct percutaneous transluminal coronary angioplasty (PTCA) and intravenous recombinant tissue plasminogen activator (rt‐PA) on left ventricular remodeling in patients with acute myocardial infarction (AMI). To address this issue, patients with AMI randomly assigned to direct PTCA or intravenous rt‐PA as part of a large multicenter study (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries [GUSTO] IIb Angioplasty Substudy) were evaluated with two‐dimensional echocardiography at predischarge. An echocardiographic infarct size index and the end‐diastolic and end‐systolic left ventricular volumes were computed. Patients with an infarct size index equal to or higher than the mean value were considered to have a large infarction. Of 26 enrolled patients, 13 were assigned to PTCA (9 successfully reperfused: i.e., TIMI‐3 flow after PTCA) and 13 to rt‐PA (10 successfully reperfused: i.e., ST resolution after rt‐PA). In patients considered successfully reperfused, end‐systolic volumes tended to be lower in PTCA patients than in rt‐PA patients (43 ± 17 cc vs 59 ± 21 cc, P = 0.09), although there were no differences in infarct size index (7.3 ± 2.8 vs 7.0 ± 2.8) and ejection fraction (52%± 10% vs 46%± 12%). End‐systolic volume depended on infarct size index in the overall patient population (r = 0.60, P = 0.007) and in rt‐PA patients (r = 0.80, P =0.005), while no correlation was found in PTCA patients. Considering patients with large AMIs, end‐systolic volumes were higher in the four patients treated with rt‐PA than in the four patients treated with direct PTCA (P < 0.01). Considering all the 26 enrolled patients, these differences were also present, but they did not reach statistical significance. In conclusion, our results suggest that, in patients with large AMIs, adequate reperfusion obtained by direct PTCA has a more marked effect in counteracting ventricular remodeling than that obtained by systemic rt‐PA. This beneficial effect of direct PTCA, independent of any reduction in regional wall‐motion abnormalities, should be taken into account when comparing the clinical value of direct PTCA with that of systemic thrornbolysis in the treatment of AMI.

Notwithstanding pharmacokinetics has greatly increased the rational approach to the drug treatment of epilepsies, about 25% of the patients do not respond to the therapy. Therefore, a great effort has been made to discover new antiepileptic drugs effective in refractory seizures. On the basis of increased knowledge of seizure pathophysiology two principal groups of drugs have been developed: the first enhancing brain GABA activity (vigabatrin); the second inhibiting excitatory amino-acids (lamotrigine and felbamate). Oxcarbazepine has the same mechanism of action as carbamazepine, whereas gabapentin's mechanism is still uncertain. The major clinical indications of these new antiepileptic drugs are represented by partial complex seizures. Side effects (mostly regarding the central nervous system) appear mild, and clinical interactions have little importance. The role of therapeutic drug monitoring for these substances is at present not well established.

A high-pressure liquid chromatographic (HPLC) method for the serum assay of benperidol is described. One ml of serum is required for a single estimation. The method involves a simple and rapid extraction step (BondElut columns), HPLC separation (C810-μ column), and electrochemical detection (± 0.65 V). Haloperidol is used as internal standard. On the basis of this procedure, recovery (93–97) and reproducibility (intra-assay and inter-assay coefficients of variation <9) are satisfactory. The detection limit is 0.2 ng/ml of serum. After therapeutic doses, trough serum levels ranged from 3.8 to 12 ng/ml in five patients.

1 A patient ingested about 5 g of orphenadrine hydrochloride. He had gastric lavage and oral administration of activated charcoal. The main symptoms were neuropsychiatric in nature.2 Possible relation between serum levels of the drug and time course of the toxic effects are described.

Since motor fluctuations in Parkinsonian patients might be, at least in part, explained by an antagonism between levodopa (LD) and its metabolite 3-O-methyldopa (3-OMD) at blood-brain-barrier (BBB), we decided to study LD and 3-OMD plasma and cerebrospinal fluid (CSF) levels in subjects undergoing lumbar puncture for diagnostic purposes. After informed consent, 70 subjects took a tablet of carbidopa-levodopa association (Sinemet or Sinemet-CR) 0.5, 1, 2, 4, 8, 12h before blood and lumbar cerebrospinal fluid collection. LD and 3-OMD were determined by an HPLC-electrochemical method. The subjects treated with Sinemet-CR had lower LD cerebrospinal fluid concentrations along with lower LD and higher 3-OMD plasma concentrations. This pattern of LD cerebrospinal fluid concentrations may be explained by means of a transport competition between LD and 3-OMD at blood brain barrier level.

Early measurement of blast clearance is a relevant prognostic indicator in childhood acute lymphoblastic leukemia (ALL). To this purpose we measured, by four-colour flowcytometry (FC), the percentage of blast cells in bone marrow samples from Italian patients enrolled in the multicentre AIEOP-BFM ALL 2000 trial. Samples were collected on day 15 (after 14 days of steroids, and one dose of IT-MTX, vincristine, daunorubicine, asparaginase) and shipped overnight to the reference laboratory. The data were compared to PCR-MRD performed, by study design, on day +33 and +78 BM samples. We report the results of patients enrolled between December 2000 and October 2004. The 561 patients studied were not different from the remaining ones (with no available material) including their cumulative incidence of relapse (SE): 17.3% (1.9) vs. 18.1% (1.5) in 850 patients not studied. According to the results of FC-MRD, 5 groups were defined: negative (blast count <0.01%, n=143), <0.1% (n=94), <1% (n=149), 1–10% (n=119), >10% (n=56). Their cumulative 5-year risk of relapse was: 4.1% (1.9), 9.3% (4.0), 14.3% (3.2), 26.5% (5.5), 53.7% (7.4), respectively. By PCR-MRD, the same patients were stratified as follows: 177 were standard risk and had 5-year risk of relapse of 4.1% (1.7), 233 at intermediate risk had a relapse risk of 24.2% (3.4), 37 at high risk had a relapse risk of 58.1% (9); the remaining 124 patients (21.6%) were not stratified by PCR-MRD due to lack of 2 sensitive (≥10−4) markers. Of 177 patients classified as standard risk by PCR (double negative), 110 fell within the 2 subgroups with lower FC-MRD (<0.1%), 46 had <1%, 19 had <10%, only 2 >10% of blasts. Of the 233 patients stratified as PCR-MRD intermediate risk (d78 <10−3), FC-MRD related groups had the following probabilities of EFS: 93.5% (3.6; n=47), 83.3%(8.0; n=30), 80.5%(5.1; n=70), 66.5%(10.8; n=57), 39.2%(11.8; n=29). We conclude that very early measurement of FC-MRD on day 15 bone marrow is feasible in our multicentre cooperative setting. On the basis of our data we suggest the following risk groups: standard, when <0.1% blasts on day 15 BM; intermediate for 0.1 to <10%; high, for >10% blasts. These groups had a risk of relapse of 6.2% (1.9), 19.5% (3), and 53.7% (7.4), respectively. Since it is fast, reproducible, relatively cheap and applicable to virtually all patients, our group decided to apply it prospectively on all ALL patients to integrate PCR-based stratification. Our findings showed that: early (d15) MRD detection by FCM identifies different patients than PCR on d33 and d78; FCM may be very useful to identify earlier the highly sensitive ALL with low relapse risk (even though long-term follow-up is still missing), whereas later timepoints may be accessible for PCR and the identification of HR patients.

Early measurement of blast clearance is a relevant prognostic indicator in childhood acute lymphoblastic leukemia (ALL). To this purpose we measured, by four-colour flowcytometry (FC), the percentage of blast cells in bone marrow samples from Italian patients enrolled in the multicentre AIEOP-BFM ALL 2000 trial. Samples were collected on day 15 (after 14 days of steroids, and one dose of IT-MTX, vincristine, daunorubicine, asparaginase) and shipped overnight to the reference laboratory. The data were compared to PCR-MRD performed, by study design, on day +33 and +78 BM samples. We report the results of patients enrolled between December 2000 and October 2004. The 561 patients studied were not different from the remaining ones (with no available material) including their cumulative incidence of relapse (SE): 17.3% (1.9) vs. 18.1% (1.5) in 850 patients not studied. According to the results of FC-MRD, 5 groups were defined: negative (blast count <0.01%, n=143), <0.1% (n=94), <1% (n=149), 1–10% (n=119), >10% (n=56). Their cumulative 5-year risk of relapse was: 4.1% (1.9), 9.3% (4.0), 14.3% (3.2), 26.5% (5.5), 53.7% (7.4), respectively. By PCR-MRD, the same patients were stratified as follows: 177 were standard risk and had 5-year risk of relapse of 4.1% (1.7), 233 at intermediate risk had a relapse risk of 24.2% (3.4), 37 at high risk had a relapse risk of 58.1% (9); the remaining 124 patients (21.6%) were not stratified by PCR-MRD due to lack of 2 sensitive (≥10−4) markers. Of 177 patients classified as standard risk by PCR (double negative), 110 fell within the 2 subgroups with lower FC-MRD (<0.1%), 46 had <1%, 19 had <10%, only 2 >10% of blasts. Of the 233 patients stratified as PCR-MRD intermediate risk (d78 <10−3), FC-MRD related groups had the following probabilities of EFS: 93.5% (3.6; n=47), 83.3%(8.0; n=30), 80.5%(5.1; n=70), 66.5%(10.8; n=57), 39.2%(11.8; n=29). We conclude that very early measurement of FC-MRD on day 15 bone marrow is feasible in our multicentre cooperative setting. On the basis of our data we suggest the following risk groups: standard, when <0.1% blasts on day 15 BM; intermediate for 0.1 to <10%; high, for >10% blasts. These groups had a risk of relapse of 6.2% (1.9), 19.5% (3), and 53.7% (7.4), respectively. Since it is fast, reproducible, relatively cheap and applicable to virtually all patients, our group decided to apply it prospectively on all ALL patients to integrate PCR-based stratification. Our findings showed that:

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