Imatinib mesylate in chordoma

BACKGROUND: To the authors' knowledge, no effective medical therapy currently is available for advanced chordoma. Imatinib mesylate is a tyrosine kinase inhibitor targeting platelet-derived growth factor receptor-beta (PDGFRB), BCR-ABL, and KIT. METHODS: Six patients with advanced chordoma were treated with imatinib mesylate at a dose of 800 mg daily. In all patients, the tumor was found to be positive for PDGFRB, and in four patients PDGFRB was shown to be phosphorylated/expressed. RESULTS: After a treatment period of > or = 1 year, overt tumor liquefaction was evident on computed tomography (CT) scan in the first patient. In previous months, a decrease in contrast enhancement on magnetic resonance imaging (MRI) and a decrease in glucose uptake on positron emission tomography (PET) were detected. Similar signs on MRI and PET were observed in subsequent patients, who had a shorter treatment period. One of these patients initially was removed from therapy and then was readmitted to therapy because of difficulties with regard to tumor response assessment; 1 month after the reinitiation of therapy, an overt decrease in tumor density was visible on CT scan in this patient. In four of five symptomatic patients, a subjective improvement was observed early in the course of treatment. The first patient died after 17 months, with a sizeable, mostly liquefied mass. Another patient died early, apparently of unrelated causes. The remaining patients were on therapy at the time of last follow-up. CONCLUSIONS: Imatinib mesylate has been found to have antitumor activity in patients with chordoma. This activity might be mediated by inactivation of PDGFRB. Tumor response manifests through patterns that are similar to those observed in patients with gastrointestinal stromal tumors who respond to molecular-targeted therapy, but evolves more slowly. The benefit to the patient entailed by this pattern of tumor response in chordoma needs to be elucidated, but may be limited in the presence of significant local disease.     

Relationships of age at onset with clinical features and cognitive functions in a sample of schizophrenia patients

BACKGROUND: A number of studies investigated the relationships of age at onset with clinical presentation and cognitive performance of schizophrenic patients. The aim of the present study was to assess demographic and clinical characteristics; psychopathologic, social functioning, and quality-of-life ratings; and neuropsychological measures in a sample of patients with stabilized schizophrenia and to identify which factors independently contributed to a multiple regression model with age at onset as the dependent variable. METHOD: Ninety-six consecutive outpatients with schizophrenia (DSM-IV-TR criteria) were included in the study. Assessment instruments were as follows: a semistructured interview, the Clinical Global Impressions scale, the Comprehensive Psychopathological Rating Scale, and the Positive and Negative Syndrome Scale (PANSS) for psycho-pathology of schizophrenia; the Calgary Depression Scale for Schizophrenia (CDSS) for depression; the Social and Occupational Functioning Assessment Scale and the Sheehan Disability Scale for social functioning; the Quality of Life Scale; and a neuro-psychological battery including the Wisconsin Card Sorting Test (WCST) and the Continuous Performance Test. Two models of multiple regression were tested: the first included clinical features and psychopathologic, social functioning, and quality-of-life scales; the second also considered neuro-psychological variables. Data were collected from October 2001 to November 2002. RESULTS: The first multiple regression showed that age at onset was significantly related to scores on the PANSS subscale for negative symptoms (p =.042) and the CDSS (p =.041); the second regression found a relation of age at onset with PANSS score for negative symptoms (p =.002) and 2 neuropsychological measures, number of preservative errors on the WCST and Continuous Performance Test reaction time (p =.0005 for both). CONCLUSION: Our data indicate that, when results of neuropsychological tests are considered, early age at onset of schizophrenia is associated with severity of negative symptoms and compromised cognitive measures of executive functioning and sustained attention.     

Evidence for both reaching and grasping activity in the medial parieto-occipital cortex of the macaque

In humans, the caudal pole of the superior parietal lobule is involved in the control of both reaching and grasping movements, whereas in monkey it is reported to be involved only in the control of reaching. Using single-unit recordings from trained macaque monkeys, we investigated whether area V6A, a visuomotor area located in the caudal part of the posterior parietal cortex, is involved in both components of prehension, the hand transport towards the visual target and the grip formation to secure the grasp. In Experiment 1, neural activity was recorded in V6A while two monkeys performed two instructed-delay reaching tasks (reach-to-point and reach-to-grasp) under controlled conditions in darkness. Fourty-five of 93 tested neurons (48%) were modulated during reach-to-point and 62% (52/84) during reach-to-grasp. In 63% of cells (51/81) neural activity was significantly different between reach-to-point and reach-to-grasp tasks, suggesting that grip formation could influence neural activity. In Experiment 2, two monkeys performed natural reach-to-grasp movements in fully lit environment; V6A neural activity and arm-hand movements were recorded by a digital camcorder and analysed frame-by-frame using a digital video technique. Thirty of the 58 tested neurons (52%) were modulated during natural prehension; about 30% of these neurons (8/30) were modulated only during the last phase of prehension, i.e. during finger flexion around the object to be grasped. This is the first direct demonstration that both reaching and grasping modulate neural activity in the caudal part of the posterior parietal cortex of the macaque. Our work suggests a strict functional homology between human and monkey superior parietal lobule.     

Oral risperidone plus oral lorazepam versus standard care with intramuscular conventional neuroleptics in the initial phase of treating individuals with acute psychosis

Although atypical antipsychotics are now considered first line treatments for schizophrenia, intramuscular (i.m.) conventional neuroleptics are often still considered necessary in emergency treatment of acute psychoses. This European, multicentre, open-label, active-controlled trial compared oral risperidone plus oral lorazepam to standard care with i.m. conventional neuroleptics with or without lorazepam in the emergency treatment of acutely psychotic patients. Patients were allowed to choose either oral risperidone (a single dose of 2 mg and 2.0-2.5 mg lorazepam; 121 patients) or standard i.m. treatment (conventional neuroleptic with or without lorazepam; 105 patients). No additional treatment was allowed for 2 h. Primary outcome was the percentage of patients with treatment success (asleep or at least much improved on Clinical Global Impression-global improvement scale) 2 h after treatment initiation. Baseline characteristics were similar in both treatment groups. Oral risperidone plus oral lorazepam was more successful at 2 h (66.9%) and significantly non-inferior compared to standard i.m. care (54.3%; P=0.0003), and the incidence of extrapyramidal symptoms (EPS) was lower (1.7%) compared to standard i.m. care (9.5%). In acutely psychotic patients requiring emergency treatment, oral risperidone/oral lorazepam was at least as effective as i.m. conventional neuroleptic treatment with or without lorazepam. Oral risperidone plus lorazepam rapidly reduces symptoms, including aggression, and causes fewer EPS.     

Malignant hypertension and cerebral haemorrhage in Seckel syndrome

Seckel syndrome is an autosomal recessive condition with severe short stature and facial and neurological anomalies. Intracranial haemorrhage, due to rupture of a cerebral aneurysm, is a very rare complication of this syndrome. Malignant hypertension may play an important role in the aetiology of the aneurysm and early detection is essential in order to prevent organ damage. Conclusion:we report a new case of Seckel syndrome associated with malignant hypertension and cerebral haemorrhage.Abbreviations BA basilar artery - MCA middle cerebral artery - PICA posterior internal cerebral artery - PICU paediatric intensive care unit - SS Seckel syndrome     

Intratumoral color Doppler analysis in endometrial carcinoma: is it clinically useful?

OBJECTIVE: The aim was to study the effectiveness of subjective color Doppler evaluation and spectral Doppler parameters in preoperative characterization of endometrial carcinomas. METHODS: Seventy-six patients with endometrial carcinoma were preoperatively analyzed by color Doppler ultrasound in order to subjectively evaluate the amount of intratumoral blood flow (color score) and to analyze the lowest resistance index (RI), the highest peak systolic velocity (PV), and the highest time averaged maximum velocity (TAMVX). These parameters were analyzed according to clinico-pathological characteristics. RESULTS: In 13 patients no intratumoral arterial vessels were detected by color Doppler examination. No lymph node metastases were found in this group of patients. Positive nodes were found in 24% of patients with detectable arterial vessels, although the difference did not reach the statistical significance. No differences were found in spectral Doppler parameters (RI, PV, TAMVX) according to tumor characteristics or nodal involvement. A higher percentage of cases with a color score of 3 was found in stage >I than in stage I patients (69 vs 42%, P < 0.05), and in patients with myometrial invasion greater than 50% than in those with less than 50% invasion (72 vs 38%; P = 0.05). CONCLUSIONS: Nodal metastases were found in 24% of patients with detectable vessels at color Doppler examination. Subjective analysis of vessel density correlated >50%, myometrial invasion, but spectral Doppler analysis was not predictive of surgical stage, tumor grade, myometrial invasion, or lymph node metastases. These results do not support the use of preoperative intratumoral blood flow analysis as a clinical test in evaluating tumor characteristics or in predicting lymph node metastases.     

Gastric surgery as a long-term risk factor for malignant lesions of the larynx

BACKGROUND: Duodenogastroesophageal reflux is common after total or partial gastrectomy. No data are available on the effect of duodenal reflux on the larynx. HYPOTHESIS: Premalignant or malignant changes occur more frequently among subjects with gastric surgery. DESIGN: Historical cohort study. SETTING: Outpatient setting for upper endoscopy. PATIENTS: Ninety-three subjects who had undergone gastric resection at least 5 years previously, and 93 matched dyspeptic individuals who did not undergo gastric surgery. INTERVENTION: Clinical histories of all patients were obtained and recorded. All subjects underwent an otolaryngologic evaluation. RESULTS: Of 93 patients with gastric resection, 7 patients had current or previous laryngeal malignancies or current precancerous mucosal changes. In the control group, 1 subject had a leukoplakia on the vocal cord. The adjusted odds ratio (having included sex, age, and alcohol [yes or no] and smoking [yes or no] history in the regression model) was 9.88 (95% confidence interval, 1.01-97.31; likelihood ratio chi2 = 28.77; P<.001). Furthermore, there was a significant increased prevalence of benign laryngeal lesions in patients with gastric resection vs the control group. CONCLUSIONS: The risk of developing laryngeal malignancies is higher for patients with gastric resection. A periodic otolaryngologic evaluation in subjects with gastric surgery may contribute to early diagnosis of laryngeal disorders.     

GM2 gangliosidosis variant B1

Variant B1 is a rare type of GM2 gangliosidosis. Clinically, it shows a wide spectrum of forms ranging from infantile to juvenile. We report the first magnetic resonance imaging (MRI) findings from three patients affected by GM2 gangliosidosis variant B1, two presenting with the infantile form and one with the juvenile form. The MRI appearances of the two patients with the infantile form disease are congruent with those reported for the early-onset type of both Tay-Sachs and Sandhoff diseases, and are characterized by early involvement of the basal ganglia and thalamus with cortical atrophy appearing later. In contrast, the patient with the juvenile form of variant B1 showed progressive cortical and white-matter atrophy of the supratentorial structures and, to a lesser extent, the infratentorial structures. No basal ganglia or thalamic anomalies were observed. Because in the adult forms of both Tay-Sachs and Sandhoff diseases a progressive cerebellar atrophy represents the only abnormality detectable, it appears that an MRI pattern peculiar to GM2 gangliosidosis can be defined. This pattern ranges from the basal ganglia injury associated with the early and severe demyelination process noted in the infantile form of the disease, to cerebellar atrophy with no supratentorial anomalies in the adult form. An “intermediate” MRI picture, with cortical atrophy and mild cerebellar atrophy, but without basal ganglia impairment, can be observed in the juvenile form. In addition, our investigations suggest that MRI abnormalities in GM2 gangliosidosis correlate with the clinical form of the disease rather than with the biochemical variant of the enzymatic defect. Received: 9 January 2002, Received in revised form: 26 June 2002, Accepted: 8 July 2002 Correspondence to Paolo Balestri, M. D.