PURPOSE: Epidermal growth factor receptor is expressed in pediatric malignant solid tumors. We conducted a phase I trial of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in children with refractory solid tumors. PATIENTS AND METHODS: Gefitinib (150, 300, 400, or 500 mg/m2) was administered orally to cohorts of three to six patients once daily continuously until disease progression or significant toxicity. Pharmacokinetic studies were performed during course one (day 1 through 28). RESULTS: Of the 25 enrolled patients, 19 (median age, 15 years) were fully evaluable for toxicity and received 54 courses. Dose-limiting toxicity was rash in two patients treated with 500 mg/m2 and elevated ALT and AST in one patient treated with 400 mg/m2. The maximum-tolerated dose was 400 mg/m2/d. The most frequent non-dose-limiting toxicities were grade 1 or 2 dry skin, anemia, diarrhea, nausea, and vomiting. One patient with Ewing's sarcoma had a partial response. Disease stabilized for 8 to > or = 60 weeks in two patients with Wilms' tumor and two with brainstem glioma (one exophytic). At 400 mg/m2, the median peak gefitinib plasma concentration was 2.2 microg/mL (range, 1.2 to 3.6 microg/mL) and occurred at a median of 2.3 hours (range, 2.0 to 8.3 hours) after drug administration. The median apparent clearance and median half-life were 14.8 L/h/m2 (range, 3.8 to 24.8 L/h/m2) and 11.7 hours (range, 5.6 to 22.8 hours), respectively. Gefitinib systemic exposures were comparable with those associated with antitumor activity in adults. CONCLUSION: Oral gefitinib is well tolerated in children. Development of the drug in combination with cytotoxic chemotherapy will be pursued. 相似文献
We report the clinicopathologic, immunohistochemical, and ultrastructural features of three small-cell neuroendocrine carcinomas of the ampullary region of the duodenum. All patients were men; their ages were 51, 62, and 66 years. The therapy consisted of pancreatoduodenectomy. All patients died of the disease; median survival was 10 months from the diagnosis. The histological appearance was identical to pulmonary and extrapulmonary small-cell carcinoma. The neuroendocrine differentiation was demonstrated ultrastructurally by the presence of dense-core granules, and by the positive immunoreaction for neuron-specific enolase and Leu-7 in each case. One case expressed a focal positivity for chromogranin A (PHE-5) and argyrophilic granules. The same case showed the presence of neurofilaments on frozen material. Neurofilament proteins could not be demonstrated in any case in paraffin sections. Neoplastic cells exhibited cytoplasmic immunostaining for cytokeratins (CAM 5.2) in all cases. In one case, a large number of neoplastic cells (60-70%) exhibited nuclear Ki-67 positivity. We postulate that the disease's histogenesis was from epithelial stem cell expressing both epithelial and neuroendocrine characteristics. The clinical behavior of small-cell neuroendocrine carcinomas of the ampullary region appears to be extremely aggressive, with early metastases and fatal outcome. 相似文献
We report a study of realimentation techniques in 9 unweaned infants with multiple food hypersensitivity. The patients had presented severe symptoms of cow's milk allergy and successive attempts using milk containing soy protein and/or a semielemental formula in their alimentation did not improve their clinical condition, due to the onset of hypersensitivity to these allergens as well. After a short period of parenteral alimentation the infants were refed per os with ass' milk (250 ml/kg/day) + medium chain triglycerides (40 ml/L milk). This food was well tolerated by all patients. No negative clinical reactions were recorded and during hospitalisation average weight increase was 39.8 g/day. The follow-up of the patients showed that ass' milk was tolerated without any problems up to an age ranging from 15 to 20 months, when cow's milk was reintroduced in some patients. 相似文献
Background: Smoking is considered to be a risk factor for patients undergoing surgery and anesthesia, but it is unclear whether this is applicable to patients undergoing ambulatory surgery. The aim of this study was to determine the risk of respiratory complications and wound infection among smokers.
Methods: The authors studied a random selection of 489 adult patients undergoing ambulatory surgery. Smoking status was determined by self-report and confirmed with end-expired carbon monoxide analysis. The risk of respiratory complications (i.e., desaturation, cough, laryngospasm, bronchospasm, breath-holding, or apnea) and wound infection (i.e., wound redness or discharge +/- positive microbial culture, requiring antibiotic therapy) in smokers versus nonsmokers was ascertained. Odds ratios were estimated from multivariable logistic regression and adjusted for age, gender, body mass index, partner's smoking status, domiciliary smoking exposure, and extent and duration of surgery.
Results: Most smokers continued to smoke up until the day of surgery. Smokers had a higher rate of respiratory complications (32.8%vs. 25.9%; adjusted odds ratio, 1.71; 95% confidence interval, 1.03-2.84;P = 0.038) and wound infection (3.6%vs. 0.6%; odds ratio, 16.3; 95% confidence interval, 1.58-175;P = 0.019). Odds ratios comparing current plus ex-smokers with nonsmokers were of similar magnitude for most of these complications. 相似文献
Summary The current interest in stereotactic posteroventral pallidotomy (PVP) for treating Parkinson's disease and the variability of published results have raised questions regarding techniques for target localization. In our technique the probe is guided to the optimum target at the most ventral pallidum and ansa lenticularis by macroelectrode stimulation of the internal capsule and optic tract from within the globus pallidus, with the thresholds providing a relative measure of the electrode proximity to these structures. We have characterized these localizing macroelectrode stimulation parameters in 57 posteroventral pallidotomies with consistent anatomic lesion placement, excellent outcome, and no complications.Using a 1.8 × 2.0 mm radiofrequency electrode for macroelectrode stimulation (RFG-3C, Radionics Inc.), minimum voltages (thresholds) to activate motor (at a frequency of 2 Hz) or visual (at a frequency of 100 Hz) responses as well as impedance measurements were obtained at the final target (Tf) and at distances proximal to Tf along the electrode trajectory. The visual and motor threshold voltages at Tf via our standard approach angles (50 ° above base plane, 20 ° from the sagittal plane), had a range of 1.0 to 1.5 V, and 2.0 to 3.5 V respectively. We also found that as the probe approaches Tf there is a significant decrease in voltage thresholds for motor (P<.0001) and visual (P<.0001) responses in an individual patient indicating that the probe is converging on these structures. Increases in impedance between Tf, 2–3 mm, and 4–5 mm proximal to Tf were also statistically significant (P<.0001). Microelectrode recording of electrophysiological neuronal activity at various points along the trajectory towards the target showed distinct firing patters providing identification of the globus pallidus externus and internus, ansa lenticularis, and optic tract.Macroelectrode electrophysiological stimulation within the target volume, inducing threshold responses in the internal capsule and optic tract, provides for accurate localization of the most effective PVP target in the ansa lenticularis. In unresponsive patients, the utilization of microelectrode recording for the identification of the pallidal borders and the optic tract improves safety. 相似文献
Almost all investigations of first-episode schizophrenia uncover more male than female subjects. Two possible explanations for this observation are (1) first-episode investigations suffer more or less consistent methodologic biases or (2) the incidence of schizophrenia is higher in men than in women. Data from the markers and predictors of schizophrenia (MAP) project, a community-based first-episode study, permitted an investigation of the two alternatives. The results suggest that neither recruitment nor diagnostic vagaries explain the excess of males. Instead, the MAP results, consistent with other recent investigations, suggest that the incidence of schizophrenia is lower in women than in men. The findings are consistent with the literature on gender differences in schizophrenia, which indicates that schizophrenia in women is a less severe disorder than in men. The report includes recommendations for future first-episode investigations to ensure adequate representation of women. 相似文献
Limited-field-of-view radio-frequency receiver antennas provide improved near-field sensitivity for magnetic resonance imaging by decreasing the antenna volume. The Helmholtz-type surface coil, consisting of two flat rings, is an organ-encompassing antenna that takes advantage of this principle to yield an improved signal-to-noise ratio (S/N). The coil was tested in a group of 50 patients and 16 healthy volunteers. Images obtained with the Helmholtz coil demonstrated quantitatively superior S/N of 2.2-fold or greater than that of comparison body coil images, as well as qualitatively superior anatomic resolution. 相似文献
To determine the usefulness of including a duration criterion in the definition of "negative" symptoms, the prognostic significance of a longitudinally obtained measure of negative symptoms was compared with a cross-sectionally obtained measure. As predicted, the presence of negative symptoms based on longitudinal observation was associated with most aspects of 18-month course in a group of "first-episode" schizophrenic individuals, whereas cross-sectional levels of negative symptoms were not. The findings suggest that negative symptoms, when operationalized as a trait-like phenomenon, help to portend a poor course of illness. 相似文献
BACKGROUND: It has been argued that lay interviewers' use of fully-structured interviews could lead to a diagnostic pattern different to that by treating physicians. Clinical interviewers in community samples should probably identify cases that are closer to those seen in clinical settings. The greatest advantage of using clinical interviewers consists of the immediate assessment of a possible psychopathology, i.e. the evaluation of current disorders. METHODS: Two thousand three hundred and sixty-three citizens from the community of Sesto Fiorentino, Italy, were interviewed by their own general practitioners using the Mini International Neuropsychiatric Interview (MINI). Positive cases for any lifetime psychiatric disorder as well as a random sample of the negative cases were re-interviewed by psychiatrists or trained residents in psychiatry using the Florence Psychiatric Interview (FPI). RESULTS: The point prevalence for any current disorder was 8.7%; the two disorders with the highest prevalence were generalised anxiety disorder (2.9%) and major depressive episode (2.7%). The figures increase about 50% when the sub-threshold sequelae of previous disorders are considered. Current comorbidity was generally high. The one-year prevalence of any disorder was 10.6%. Ninety-two percent of the cases sought help, 82% were being treated at the moment of interview. Social impairment was considerable. CONCLUSIONS: The period prevalence rates for most of the disorders considered were generally comparable with the range defined by previous studies conducted in other Western countries, despite using different methodologies. Conversely, the use of health facilities, the treatment received and the social impairment were much higher than those reported by the other studies, suggesting a greater similarity with the clinical samples. 相似文献