Background: Measuring the work of breathing of patients undergoing spontaneous assisted ventilation can be useful to monitor and titrate ventilatory support. The aim of this study was to obtain measurements of the pressure generated by the respiratory muscles (PMUSC) and the derived pressure-time product (PTP; a good indicator of the metabolic work of breathing), performing the rapid interrupter technique with a commercial ventilator.
Methods: A Draeger Evita 4 ventilator (Draeger Medical, Lubeck, Germany) was controlled by a personal computer to rapidly interrupt the airway flow at different times and volumes of the respiratory cycle during pressure-support ventilation. From the airway pressure tracing after the occlusion, the authors estimated the alveolar pressure and PMUSC; the integration of PMUSC values over the inspiratory time yields the measurement of PTP. Esophageal pressure measurements were used as a reference. After a bench study of the valves' performance, the authors performed 11 measurement sequences in eight patients.
Results: The closure times for the inspiratory and expiratory valves were 74 +/- 10 and 61 +/- 13 ms, respectively. The interrupter technique provided a reliable estimate of PMUSC (PMUSC, occl = 1.00 [middle dot] PMUSC, pes + 0.19; r = 0.88; 95% confidence interval for agreement, +5.49/-5.32 cm H2O). PTPoccl tightly correlated with PTPpes (PTPoccl = 0.95 [middle dot] PTPpes + 0.13; r = 0.96; 95% confidence interval, 1.94/-1.61 cm H2O [middle dot] s). 相似文献
PURPOSE: Fenretinide (4HPR), a synthetic retinoid, induces apoptosis in neuroblastoma cells. A Phase I study in children with neuroblastoma was designed to determine maximum tolerated dose, toxicity, and pharmacokinetics. EXPERIMENTAL DESIGN: Fifty-four patients received oral 4HPR, once daily, for 28 days, followed by a 7-day interruption, for up to 6 courses. The starting dose was 100 mg/m(2)/day. At least 3 patients were entered at each escalating 4HPR dose level. Pharmacokinetic sampling was performed on days 1 and 28 of the first course. RESULTS: Fifty-four patients, of whom 53 were evaluable, received doses between 100 and 4000 mg/m(2)/day for a total of 168 courses. Additional dose escalation was precluded by capsule number intake. A total of 34 of 53 evaluable patients showed manageable, reversible toxicities, which were not dose related. One dose-limiting toxicity (nyctalopia grade 3) occurred after the 1000 mg/m(2)/day dose. Twelve patients showed grade 2 toxicity: skin xerosis (6 cases); nyctalopia (3 cases); hepatic toxicity (1 case); diarrhea (1 case); and headache (1 case). Stable disease was observed in 41 patients for a median period of 23 months (range 2-35+). After first administration, average 4HPR peak plasma levels ranged from 0.6 to 6 micro M (after 100 and 4000 mg/m(2)/day, respectively) and increased 2-fold (to 1.3 and 12.9 micro M, respectively) after the 28-day treatment. 4HPR half-life increased from 17 h after the first administration to 25 h after the 28(th) administration. Incidence of grade 2-3 toxicity was 0 of 12 (0%), 7 of 22 (31%), and 4 of 8 (50%) with peak 4HPR concentrations <3 micro M, 3-10 micro M, and >10 micro M, respectively. After repeated treatment, retinol levels decreased from 20 to 10% of pretreatment levels after all of the doses. CONCLUSIONS: In children, 4HPR administration up to 4000 mg/m(2)/day over 28 days, followed by a 7-day interruption, results in manageable toxicity and in drug plasma concentrations comparable with those that induce apoptosis in neuroblastoma cell lines. 相似文献
Schizophrenia (SCZ) and bipolar disorder (BD) share some cognitive commonalities. However, the role of associative learning, which is a cornerstone of human cognition mainly relying on hippocampus, has been under-investigated. We assessed behavioral performance during associative learning in a group of SCZ, BD and healthy controls (HC).
Methods
Nineteen patients with SCZ (36 ± 8.1 years; 13 males, 6 females; all Caucasians), 14 patients with BD (41 ± 9.6 years; 5 males, 9 females; all Caucasians) and 45 HC (27.7 ± 6.9 years; 18 males, 27 females; all Caucasians) were studied. Learning was assessed using an established object-location paired-associative learning paradigm. Subjects learned associations between nine equi-familiar common objects and locations in a nine-location grid. Performance data were analyzed in a repeated measures analysis of variance with time (repeated) and group as factors.
Results
Learning curves (performance = 1−e−k?time) fitted to average performance data in the three groups revealed lower learning rates in SCZ and BD (k = 0.17 and k = 0.34) than HC (k = 0.78). Significant effects of group (F = 11.05, p < 0.001) and time (F = 122.06, p < 0.001) on learning performance were observed.
Conclusions
Our study showed that associative learning is impaired in both SCZ and BD, being potentially not affected by medication. Future studies should investigate the neural substrates of learning deficits in SCZ and BD, particularly focusing on hippocampus function and glutamatergic transmission. 相似文献
Background:Alveolar soft part sarcoma (ASPS) is a rare malignanttumor and little is known about its clinical features and management. Wereport on a series of 19 pediatric patients managed over 20 years.
Patients and methods:Primary conservative surgery was performedin all patients and was radical in nine, non-radical in three; seven patientsunderwent biopsy alone (3 unresectable tumors, 4 metastatic disease). In twocases radical surgery was performed after primary chemotherapy. Radiotherapywas delivered to 8 patients, chemotherapy to 15.
Results:After a median follow-up of 74 months, the five-yearsurvival was 80% for the whole series, 91% for patients withlocalized disease, 100% for patients with tumor 5 cm, and31% for those >5 cm; 16 of 19 patients were alive (12 of 12 withgrossly-resected tumor in first continuous remission). Chemotherapy achievedtwo partial remission among seven evaluable patients.
Conclusions:Pediatric ASPS has a more favorable prognosis thanits adult counterpart. In this series, tumor size correlates with metastaticdisease at onset and is the major factor influencing survival. Surgery is themainstay of therapy. The effectiveness of adjuvant therapy remains to beestablished, though radiotherapy may be advisable in cases of inadequatesurgery. 相似文献
The objective of this study was to examine whether anxiety increases impulsivity among patients with bipolar disorder (BPD) and major depressive disorder (MDD). Subjects comprised 205 BPD (mean age ± SD 36.6 ± 11.5 y; 29.3% males) and 105 with MDD (mean age ± SD 38 ± 13.1 y; 29.5% males) diagnosed using the DSM-IV-SCID. Impulsivity was assessed with the Barratt Impulsivity Scale and anxiety with the Hamilton Anxiety Rating Scale. Comorbid anxiety disorders were present in 58.9% of the BPD and 29.1% of MDD. BPD were significantly more impulsive than MDD (p < 0.001), and both BPD and MDD subjects showed significantly higher impulsivity when anxiety was present either as a comorbidity (p = 0.010) or as a symptom (p = 0.011). Impulsivity rose more rapidly with increasing anxiety symptoms in MDD than in BPD. The presence of anxiety, either as a comorbid disorder or as current anxiety symptoms, is associated with higher impulsivity in subjects with either BPD or MDD. 相似文献
Neural tumors, Wilms' tumor, rhabdomyosarcoma and several types of leukemia have been previously described in association with neurofibromatosis (NF). In a nation-wide collection of cases in Italy, 15 children (0-14 years of age) with NF and cancer or leukemia were identified; 13 of them had been diagnosed with cancer between 1976-83. The expected number of children with cancer and NF in 1976-83 was 4.48. The distribution of tumor types was different from that found in the general population, with a higher proportion of tumors of neural crest origin as well as soft tissue sarcomas. In 7/15 the family history was positive for NF; in 5/7 the individuals affected included the mother and/or a maternal relative. 相似文献
Brain atrophy has consistently been observed in schizophrenia, representing a 'gross' evidence of anatomical abnormalities. Reduced cerebral blood volume (CBV) may accompany brain size decrement in schizophrenia, as suggested by prior small SPECT studies. In this study, we non-invasively investigated the hemisphere CBV in a large sample of patients suffering from schizophrenia with perfusion-weighted imaging (PWI). PWI images were obtained, following intravenous injection of paramagnetic contrast agent (Gadolinium-DTPA), for 54 DSM-IV patients with schizophrenia (mean age+/-SD=39.19+/-12.20 years; 34 males, 20 females) and 24 normal controls (mean age+/-SD=44.63+/-10.43 years; 9 males, 15 females) with a 1.5T Siemens magnet using an echo-planar sequence (TR=2160 ms, TE=47 ms, slice thickness=5mm). The contrast of enhancement (CE), a semi-quantitative parameter inversely estimating the CBV, were calculated pixel by pixel as the ratio of the maximum signal intensity drop during the passage of contrast agent (Sm) by the baseline pre-bolus signal intensity (So) (CE=Sm/Sox100) for right and left hemisphere on two axial images. Specifically, higher CE values correspond to lower CBV and viceversa Compared to normal controls, patients with schizophrenia had significantly higher bilateral hemisphere CE values (p=0.02) and inverse CE laterality index (p=0.02). This study showed abnormally reduced and inverse hemisphere CBV in a large population of patients with schizophrenia. Hypothetically, chronic low CBV may sustain neural hypoactivation and concomitant increase of free radicals, ultimately resulting in neuronal loss and cognitive impairments. Thus, altered intracranial hemodynamics may accompany brain atrophy and cognitive deficits, being a crucial factor in the pathophysiology of schizophrenia. 相似文献
BACKGROUND: Measuring the work of breathing of patients undergoing spontaneous assisted ventilation can be useful to monitor and titrate ventilatory support. The aim of this study was to obtain measurements of the pressure generated by the respiratory muscles (PMUSC) and the derived pressure-time product (PTP; a good indicator of the metabolic work of breathing), performing the rapid interrupter technique with a commercial ventilator. METHODS: A Draeger Evita 4 ventilator (Draeger Medical, Lubeck, Germany) was controlled by a personal computer to rapidly interrupt the airway flow at different times and volumes of the respiratory cycle during pressure-support ventilation. From the airway pressure tracing after the occlusion, the authors estimated the alveolar pressure and PMUSC; the integration of PMUSC values over the inspiratory time yields the measurement of PTP. Esophageal pressure measurements were used as a reference. After a bench study of the valves' performance, the authors performed 11 measurement sequences in eight patients. RESULTS: The closure times for the inspiratory and expiratory valves were 74 +/- 10 and 61 +/- 13 ms, respectively. The interrupter technique provided a reliable estimate of PMUSC (PMUSC, occl = 1.00 . PMUSC, pes + 0.19; r = 0.88; 95% confidence interval for agreement, +5.49/-5.32 cm H2O). PTPoccl tightly correlated with PTPpes (PTPoccl = 0.95 . PTPpes + 0.13; r = 0.96; 95% confidence interval, 1.94/-1.61 cm H2O . s). CONCLUSION: The rapid interrupter technique can be performed by means of a commercial ventilator, providing reliable measurement of PMUSC and PTP. 相似文献
Intubation is necessary in 7 to 20% of patients with severe acute cardiogenic pulmonary oedema despite optimal treatment. This study evaluated the usefulness of parameters largely available in clinical practice to predict the need for intubation in a population of acute cardiogenic pulmonary oedema patients treated with medical therapy and continuous positive airway pressure. The present retrospective cohort study involved 142 patients with severe acute cardiogenic pulmonary oedema who were admitted to coronary care or the intensive care unit of a university hospital and were treated by an in-hospital protocol. Physiological measurements and blood gas samples were evaluated at 'baseline' (just after admission), 'early' (one to three hours after beginning treatment) and 'late' (eight to 10 hours after beginning treatment). Twenty-two patients (15.5%) required intubation. A systolic blood pressure at admission lower than 140 mmHg was significantly associated with a higher risk for intubation, while hypercapnic patients or those with a reduced left ventricular ejection fraction at admission did not show a worse prognosis. A simple score based on largely available parameters (1 point for each: age >78 years, systolic blood pressure <140 mmHg at admission, arterial blood gas acidosis and heart rate >95 bpm at early time) is proposed. The rate of intubation according to this score ranged from 0% (score of 0) to 90% (score of 3). Our study found that simple parameters available in clinical practice are significantly associated with the need for intubation in acute cardiogenic pulmonary oedema patients treated with continuous positive airway pressure and medical therapy. A simple score to evaluate the need for endotracheal intubation is proposed. 相似文献