Interphase cytogenetics for the detection of the t(11;22)(q24;q12) in small round cell tumors.

Among the small round cell tumors differential diagnosis is particularly difficult for their undifferentiated or primitive character. In this mixed group of tumors, only the primitive neuroectodermal tumors, which include Ewing's sarcoma (ES), show the unique and consistent feature of the (11;22)(q24;q12) translocation, which can therefore be considered a hallmark of these neoplasias. We analyzed four primitive neuroectodermal tumor cell lines, one osteosarcoma cell line, and 11 patients by fluorescent in situ hybridization with cosmid clones 23.2 and 5.8, bracketing the t(11;22) at 11q24. Metaphase spreads from tumor cell lines, and from biopsy specimens of three patients with ES were analyzed. In the remaining eight patients comprising five ES, two small cell osteosarcomas and one chronic osteomyelitis, only nuclei preparations were available for analysis. We detected the t(11;22) in interphase nuclei of the four primitive neuroectodermal tumor cell lines, of three patients in which the karyotype demonstrated the translocation and in five cases of ES in which cytogenetic analysis had not been possible. Two cases of small cell osteosarcoma and one chronic osteomyelitis were also analyzed and were both normal with respect to the t(11;22). By analyzing cell lines and small round cell tumor samples by fluorescent in situ hybridization, we established that interphase cytogenetics is a rapid alternative to chromosomal analysis for the detection of the t(11;22) and represents an invaluable tool for the differential diagnosis of small round cell tumors.     

Cost effectiveness of fluvoxamine in the treatment of recurrent depression in France.

OBJECTIVE: The objective of this study was to examine the cost effectiveness of fluvoxamine compared with tricyclic antidepressants (TCAs) in the treatment of patients with depressive episodes. DESIGN AND SETTING: A Markov process model was constructed to model the effectiveness, as measured by time without depression, and the costs of both treatments. The model examined a period of 18 months in order to capture the influence of both relapses and recurrences on the outcomes. Data for the construction of the model came from the published literature, an expert panel and a large multicentre randomised clinical trial. Costs were obtained from published sources. The setting for this study was France. MAIN OUTCOME MEASURES AND RESULTS: The results of the baseline analysis showed that the use of fluvoxamine in the maintenance treatment (recurrence prevention) of depressive disorders was less costly than TCAs with total costs (direct and indirect costs) of 40,232.40 French francs (FF) and FF52,257.53, respectively (1996 values). In addition, due to the prevention of relapse and recurrence, effectiveness favoured fluvoxamine as it was associated with a longer period of time without depression when compared with TCAs (79% of the study period vs 71%). Sensitivity analyses confirmed the robustness of these findings. CONCLUSION: In conclusion, on the basis of the assumptions used in the model, the use of fluvoxamine as maintenance therapy is clinically and economically justified in patients with depressive disorders.     

Neonatal stroke: Clinical characteristics and cerebral blood flow velocity measurements

The clinical courses of 8 term infants with focal cerebral infarction or neonatal stroke were studied to determine whether such infants can be identified by current markers of perinatal distress, and whether changes in cerebral blood flow velocity (CBFV) occur during the acute phase of the disease. CBFV was measured from the middle cerebral artery (MCA) and anterior cerebral artery (ACA) utilizing duplex Doppler. Seven of the 8 patients required no resuscitation in the delivery room; 1 infant required brief bag and mask ventilation. No infant had evidence of severe fetal acidemia (i.e., cord pH <7). All 8 infants were initially admitted to the newborn nursery. Infants were identified on the basis of abnormal clinical findings observed during the first 48 hours: seizures (n = 6) and hypotonia and apnea (n = 2). Serum electrolytes, calcium, magnesium, and glucose levels were normal, and the sepsis evaluation including a spinal tap was sterile in all patients. Neuroimaging revealed nonhemorrhagic left focal MCA infarction (n = 6) and right focal MCA infarction (n = 2). Duplex Doppler demonstrated transient ipsilateral decreases in CBFV as compared to the contralateral unaffected side at clinical presentation in 4 infants. In 2 of these infants the decrease in CBFV involved both the MCA and ACA, and in 2 infants, only the MCA vessels. These side-to-side differences were not present at subsequent CBFV measurements. The data indicate that infants who develop neonatal stroke cannot be distinguished from infants who do not develop the lesion by current markers of perinatal distress. Because neonatal stroke frequently occurs as an unanticipated event, prevention may not be possible.     

Selective application of cervical spine radiography in alert victims of blunt trauma: a prospective study

Four hundred sixty-seven adult victims of blunt trauma undergoing cervical spine radiography (CSR) were prospectively studied to identify any clinical parameters which would aid in the selective application of CSR. Eight persons (1.7%), six of whom were alert and two who presented comatose, sustained cervical spine injuries. In this study, persons injured in falls demonstrated a statistically significant greater risk of cervical spine injury compared to those injured in motor vehicle accidents (p = 0.001). In alert trauma victims, a statistical correlation with cervical spine injury was noted for individuals who had complaints of neck discomfort (p = 0.028) and for patients who manifested tenderness to neck palpation (p = 0.000039). No cervical spine injury was noted in any alert, not intoxicated, neurologically intact patient who had no complaints of neck discomfort upon questioning or palpation. We conclude that alert trauma victims with no complaints of neck discomfort upon questioning and with no tenderness on neck palpation need not undergo CSR.     

Factors affecting in vitro protein binding of etoposide in humans.

Clinical studies have demonstrated that the plasma protein binding of etoposide, a widely used anticancer drug, is extensive (approximately 94%), highly variable among patients (10-fold range), and significantly related to serum albumin and total bilirubin concentration. The present study was designed to more thoroughly evaluate factors likely to affect etoposide protein binding under controlled in vitro conditions where single variables could be changed. Protein binding was determined using an equilibrium dialysis method with tritiated etoposide. The binding of etoposide was similar in serum or plasma, and heparin had no effect on binding. Etoposide binding decreased with increased pH, but no clinically significant difference was noted within the range of physiologic pH. Etoposide binding evaluated in single-source donor plasma was concentration-dependent over a concentration range of 1 to 250 micrograms/mL. Etoposide binding parameters determined in normal human plasma were characterized by a single class of binding sites of moderate affinity (K = 2.88 +/- 0.47 x 10(4)) and high capacity (nP = 5.07 +/- 0.5 x 10(-4); where n is the number of binding sites). The etoposide binding ratio was significantly correlated with albumin concentration (r2 = 99%, p less than 0.05). The characteristics of etoposide binding in a 4.0-g/dL solution of human serum albumin (K = 3.56 +/- 1.22 x 10(4) and nP = 5.58 +/- 0.16 x 10(-4)) suggest that the single class of binding sites is on albumin. Bilirubin caused a significant decrease in K, consistent with competitive binding, but only at higher bilirubin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibition of human red blood cell glutathione reductase by valproic acid.

Glutathione reductase (GR) one of the enzymes of the glutathione redox cycle, plays a salient role in maintaining appropriate cellular levels of reduced glutathione. The enzyme in human red blood cells is inhibited in vitro by the anticonvulsant drug valproic acid (VPA). The inhibition is dose-dependent, reversible, uncompetitive and does not depend on the redox state of the enzyme. VPA also inhibits red blood cell GR activity in children being treated with the drug. The level of serum VPA correlates significantly with the suppression of GR activity.     

Of fat and fascia: Clinical conundrum corner

A case report involving a 76-year-old male is presented. The signs and symptoms represent a difficult diagnostic problem. The physical signs are dependent on a knowledge of the distribution of fat and fascia in the region involved. The importance of this distribution, both physiologic and pathologic, is the subject of a brief commentary. © 1995 WiIey-Liss, Inc.     

Guidelines for using quantitative measures of brain magnetic resonance imaging abnormalities in monitoring the treatment of multiple sclerosis

The change of brain lesion load, measured on T₂-weighted magnetic resonance imaging (MRI) using computer-assisted techniques, is a widely used secondary endpoint for phase III clinical trials in multiple sclerosis (MS). Collections, transfer, and analysis of the electronic data across multiple centers have all proved challenging and give rise to potential errors. However, many new acquisition schemes and postprocessing techniques have been developed; these may reduce scan times and result in better lesion conspicuity or lessen the human interaction needed for data analysis. This review considers many aspects of the use of MRI in clinical trials for MS and provides international consensus guidelines, derived from a task force of the European Magnetic Resonance Networks in Multiple Sclerosis (MAGNIMS) together with a group of North American experts. The main points considered are the organization of correctly powered trials and selection of participating sites; the appropriate choice of pulse sequences and image acquisition protocol given the current state of technology; quality assurance for data acquisition and analysis; accuracy and reproducibility of lesion load assessments; and the potential for the application of quantitative methods to other MRI-derived measures of disease burden.