Molecular follow-up of disease progression and interferon therapy in chronic myelocytic leukemia

We previously reported that the abl promoter (Pa) undergoes de novo DNA methylation in the course of chronic myelocytic leukemia (CML). The clinical implications of this finding are the subject of the present study in which samples of CML patients, including a group treated with interferon alpha (IFNalpha) were surveyed. The methylation status of the abl promoter was monitored by polymerase chain reaction (PCR) amplification of the Pa region after digestion with several site-methylation sensitive restriction enzymes. Some 74% of the DNA samples from blood and marrow drawn in the chronic phase were nonmethylated, similar to control samples from non-CML patients. The remaining 26% were partially methylated in the abl Pa region. The latter samples were derived from patients who were indistinguishable from the others on the basis of clinical presentation. Methylated samples were mostly derived from patients known to have a disease of longer duration (26 months v 7.5 months, P = .01). Samples of 30 IFNalpha-treated patients were sequentially analyzed in the course of treatment. Fifteen patients with no evidence of Pa methylation before treatment remained methylation-free. The remainder, who displayed Pa methylation before treatment, reverted to the methylation-free status. The outcome is attributed to IFNalpha therapy, as the Pa methylation status was not reversed in any of the patients treated with hydroxyurea. Methylation of the abl promoter indicates a disease of long-standing, most likely associated with a higher probability of imminent blastic transformation. It appears to predict the outcome of IFNalpha therapy far better than the cytogenetic response.     

Another false alarm? apnea monitor activation in a Neonatal Intensive Care Unit graduate

Neonatal emergencies have become more common as increasingly sophisticated Neonatal Intensive Care Units graduate lower birth-weight babies born at younger gestational ages. These patients present a number of challenges to emergency physicians. They are often discharged with apnea monitors, which generate a high number of false alarms. Neonatal Intensive Care Unit graduates, however, are predisposed to a number of conditions that can result in true episodes of apnea. We present such a case and will discuss the unusual underlying cause of apnea, the utility of apnea monitors, and the need for emergency physicians to be prepared to evaluate and treat these potentially complicated patients.     

Transoesophageal echocardiographic assessment of haemodynamic function during laparoscopic cholecystectomy

We have measured cardiovascular changes associated with insufflation of carbon dioxide and the reverse Trendelenburg position during laparoscopic cholecystectomy, using transoesophageal echocardiography in 13 healthy patients. End-tidal carbon dioxide values increased after insufflation of carbon dioxide, with values significantly (P < 0.05) increased after lateral tilt positioning. Creation of a pneumoperitoneum was associated with increases (P < 0.05) in left ventricular end-systolic wall stress, concomitant with increases (P < 0.01) in peak airway pressure and systemic arterial pressure. In addition, left ventricular end-diastolic area decreased (P < 0.05) after reverse Trendelenburg positioning. Left ventricular ejection fraction was maintained throughout the study.     

Intramuscular ceftriaxone compared with oral amoxicillin-clavulanate for treatment of acute otitis media in children

Two hundred and fifteen children aged 4 months 6 years with acute otitis media (AOM) were randomized to be treated either by a single i.m. injection of ceftriaxone, 50 mg/kg, with a second dose in the event of unsatisfactory response after 48 h or a history of recurrent AOM (109 patients) or amoxicillin clavulanate 12.5 mg tid (106 patients). The failure rate was similar in children treated by ceftriaxone and amoxicillin clavulanate, 4.6% and 4.7%, respectively (standard error for intergroup difference -2.87%, 95% confidence interval -5.62% to 5.87%). No significant differences between the groups were found in the dynamics of the resolution of the acute symptomatology, otoscopy findings, relapse rate at 30 days or tympanographic evidence of middle ear effusion at the scheduled visits on days 30, 60 and 90. Recurrence of AOM between days 31 and 90 was observed significantly in more children treated with amoxicillin clavulanate than with ceftriaxone--25 out of 84 (29.4%) versus 11 out of 81 (13.6%) (P = 0.012). Conclusion: Ceftriaxone injection(s) is as efficient at least as 10-day oral amoxicillin clavulanate for treatment of acute otitis media in children. Although not recommended as routine, ceftriaxone can be considered in the management of acute otitis media under special circumstances, particularly in cases when the ability to tolerate or absorb oral drugs is compromised, in children refusing or unable to take oral therapy or when the compliance is questionable.     

Anxiety disorders of childhood, Implications for adult psychopathology

Although the exact path of acquisition remains incompletely understood, research supports the association between anxiety disorders in children and psychopathologic conditions in adults. This article addresses this relationship; reviews findings on the temperamental profile and behavioral inhibition, which may be an early identifiable childhood predictor of later anxiety disorders; and discusses the importance of early intervention.     

Effective components of TORDIA cognitive–behavioral therapy for adolescent depression: Preliminary findings.

In this report, we conducted a secondary analysis of the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study to explore the impact of specific cognitive–behavioral therapy (CBT) treatment components on outcome. In TORDIA, 334 youths (ages 12 to 18 years) with major depressive disorder who had failed to respond to an adequate course of selective serotonin reuptake inhibitor (SSRI) medication were randomized to a medication switch (either to an alternative SSRI or venlafaxine) with or without 12 weeks of adjunctive CBT. Participants who had more than 9 CBT sessions were 2.5 times more likely to have adequate treatment response than those who had 9 or fewer sessions. CBT participants who received problem-solving and social skills treatment components, controlling for number of sessions and other confounding variables, were 2.3 and 2.6 times, respectively, more likely to have a positive response. These preliminary findings underscore the importance of receiving an adequate number of sessions to attain an adequate clinical response. Finally, social skills and problem solving may be active elements in CBT for adolescent depression and should be considered in treatment by those working with seriously depressed youths. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive behavioral therapy for 4- to 7-year-old children with anxiety disorders: A randomized clinical trial.

Objective: To examine the efficacy of a developmentally appropriate parent–child cognitive behavioral therapy (CBT) protocol for anxiety disorders in children ages 4–7 years. Method: Design: Randomized wait-list controlled trial. Conduct: Sixty-four children (53% female, mean age 5.4 years, 80% European American) with anxiety disorders were randomized to a parent–child CBT intervention (n = 34) or a 6-month wait-list condition (n = 30). Children were assessed by interviewers blind to treatment assignment, using structured diagnostic interviews with parents, laboratory assessments of behavioral inhibition, and parent questionnaires. Analysis: Chi-square analyses of outcome rates and linear and ordinal regression of repeated measures, examining time by intervention interactions. Results: The response rate (much or very much improved on the Clinical Global Impression Scale for Anxiety) among 57 completers was 69% versus 32% (CBT vs. controls), p     

Characterization of circulating erythrocytes from myelodysplastic patients treated with recombinant human erythropoietin

Age-density fractionation, in-vitro erythrophagocytosis, and enumeration of membrane-bound antibodies were monitored for circulating red blood cells (RBC) from five anemic patients with myelodysplastic syndromes (MDS), in relation to administration of recombinant human erythropoietin (rhEPO). The density distribution patterns of erythrocytes from the patients prior to treatment were in accordance with their inability to produce compensating levels of circulating RBC. The complete response of one patient to rhEPO and partial responses of two other patients were accompanied by shifts to larger proportions of low density (young) RBC. In vitro phagocytosis of density-fractionated RBC from the complete responder was similar to those of age-matched non-anemic donors. Elevated erythrophagocytosis prior to rhEPO administration was observed for the partial responders and further increased during treatment in one, suggesting the stimulation of abnormal progenitors producing highly defective erythrocytes. There was no correlation between levels of erythrophagocytosis and RBC membrane-bound immunoglobulins in this group of patients. Our findings suggest that density distribution analysis of circulating RBC coupled with in vitro erythrophagocytosis may provide useful predictive tools for selecting potential responders to rhEPO administration among anemic MDS patients.