Iatrogenic illness in pediatric critical care

Iatrogenic illness may be an important determinant of the need for pediatric intensive care. We prospectively evaluated consecutive admissions to a pediatric ICU (PICU) over two time periods totaling 6 months. Twenty-five (4.6%) admissions were necessitated by iatrogenic illnesses. Drug-induced conditions accounted for eight (32%) of the iatrogenic patients, and complications of medical-surgical acts accounted for 17 (68%). Diagnoses included six respiratory failures due to seizure medications, six chronic upper airway complications of neonatal intensive care, four posttonsillectomy and postadenoidectomy complications, two chronic postcardiac surgery complications, two cardiac catheterization complications, and five miscellaneous conditions. One (3.7%) patient with iatrogenic illness died. As a group, patients with iatrogenic illness were at a risk of dying similar to other patients. We conclude that iatrogenic illness is a significant cause of PICU admission.     

Adalimumab for maintenance treatment of Crohn's disease: results of the CLASSIC II trial

BACKGROUND: Adalimumab induced clinical remission after four weeks in patients with active Crohn's disease in the CLASSIC I trial. OBJECTIVE: To evaluate long term efficacy and safety of adalimumab maintenance therapy in Crohn's disease in a follow-on randomised controlled trial (CLASSIC II). METHODS: In the preceding CLASSIC I trial, 299 patients with moderate to severe Crohn's disease naive to tumour necrosis factor antagonists received induction therapy with adalimumab 40 mg/20 mg, 80 mg/40 mg, or 160 mg/80 mg, or placebo, at weeks 0 and 2. In all, 276 patients from CLASSIC I enrolled in CLASSIC II and received open-label adalimumab 40 mg at weeks 0 (week 4 of CLASSIC I) and 2; 55 patients in remission at both weeks 0 and 4 were re-randomised to adalimumab 40 mg every other week, 40 mg weekly, or placebo for 56 weeks. Patients not in remission at both weeks 0 and 4 were enrolled in an open-label arm and received adalimumab 40 mg every other week. With non-response or flare, these patients could have their dosages increased to 40 mg weekly. Patients in the randomised arm with continued non-response or disease flare could switch to open-label adalimumab 40 mg every other week and again to 40 mg weekly. The primary end point was maintenance of remission (CDAI <150) in randomised patients through week 56. RESULTS: Of 55 patients randomised at week 4, 79% who received adalimumab 40 mg every other week and 83% who received 40 mg weekly were in remission at week 56, v 44% for placebo (p<0.05). In all, 204 patients entered the open-label arm. Of these, 93 (46%) were in clinical remission at week 56. Adalimumab was generally well-tolerated in all patients. CONCLUSIONS: Adalimumab induced and maintained clinical remission for up to 56 weeks in patients with moderate to severe Crohn's disease naive to anti-TNF treatment.     

Disability and suicidal behaviors among women of reproductive age

Archives of Women's Mental Health - Limited research exists on suicidal behaviors among women with disabilities. This study examined disability, suicidal behaviors, and associated health...     

Acute pain crisis in a patient with sickle cell disease undergoing ovarian simulation for fertility preservation prior to curative stem cell transplantation: case report and literature review

Purpose

Hematopoietic stem cell transplantation (HSCT) is a cure for sickle cell disease (SCD) but frequently results in permanent sterility. The complications associated with oocyte cryopreservation and risks of future pregnancy are increased in SCD patients. This case report discusses risk reduction strategies and includes a literature review of pregnancy after HSCT.

Case

A 23-year-old woman underwent ovarian stimulation for fertility preservation resulting in cancelation due to acute pain crisis. She underwent a successful oocyte retrieval after exchange transfusion to decrease her hemoglobin S to 30%. This is the second report of a pain crisis in a woman with SCD undergoing oocyte banking.

Conclusion(s)

Women with SCD undergoing fertility preservation may be at increased risk of complications from ovarian stimulation. Risks in pregnancy after HSCT should also be considered before proceeding with fertility preservation.

     

Expression of tumor-associated antigens in acute myeloid leukemia: Implications for specific immunotherapeutic approaches

The expression of tumor-associated antigens (TAAs) might play a critical role in the control of minimal residual disease (MRD) in acute myeloid leukemia (AML), and therefore might be associated with clinical outcome in AML. In a DNA microarray analysis of 116 AML samples, we found a significant correlation between high mRNA levels of G250/CA9 and longer overall survival (P = .022), a similar trend with high mRNA levels of PRAME (P = .103), and a hint for RHAMM/HMMR. In contrast, for other TAAs like WT1, TERT, PRTN3, BCL2, and LAMR1, we found no correlation with clinical outcome. High expression of at least 1 of the 3 TAAs, RHAMM/HMMR, PRAME, or G250/CA9, provided the strongest favorable prognostic effect (P = .005). Specific T-cell responses were detected in 8 (47%) of 17 patients with AML in complete remission for RHAMM/HMMR-R3 peptide, in 7 (70%) of 10 for PRAME-P3 peptide, and in 6 (60%) of 10 for newly characterized G250/CA9-G2 peptide, a significant increased immune response compared with patients with AML patients who had refractory disease (P < .001). Furthermore, we could demonstrate specific lysis of T2 cells presenting these epitope peptides. In conclusion, expression of the TAAs RHAMM/HMMR, PRAME, and G250/CA9 can induce strong antileukemic immune responses, possibly enabling MRD control. Thus, these TAAs represent interesting targets for polyvalent immunotherapeutic approaches in AML.     

Effect of sarcomere length on step size in relaxed rabbit psoas muscle

Recent experiments have shown that shortening and stretching of sarcomeres in single activated and unactivated myofibrils occur in stepwise fashion (Yang et al. (1998) Biophys J 74: 1473-1483; Blyakhman et al. (2001) Biophys J 81: 1093-1100; Yakovenko et al. (2002) Am J Physiol Cell Physiol 283: 735-742). Here, we carried out measurements on single myofibrils from rabbit psoas muscle to investigate steps in unactivated specimens in more detail. Activated and unactivated myofibrils were released and stretched in ramp-like fashion. The time course of length change in the single sarcomere was consistently stepwise. We found that in the unactivated myofibrils, step size depended on initial sarcomere length, diminishing progressively with increase of initial sarcomere length, whereas in the case of activated sarcomeres, step size was consistently 2.7 nm.     

Airway eosinophilia and expression of interleukin-5 protein in asthma and in exacerbations of chronic bronchitis

Background An increased nutnber of eosinophils in the bronchial mucosa has been demonstrated both in asthma and in exacerbations of chronic bronchitis. Oiyective To investigate whether the airway eosinophilia present in asthma and in chronic bronchitis during exacerbations is associated with interleukin (IL)-5 protein expression in the bronchial mucosa. Methods We obtained bronchial biopsies in 18 subjects with asthma (four intrinsic, seven extrinsic and seven occupational) and in II subjects with chronic bronchitis examined during an exacerbation. The findings were compared wilh those of bronchial biopsies from 10 subjects with chronic bronchitis examined under baseline conditions and from seven normal subjects, taken as controls. By immunohistochemistry, we assessed the expression of IL-5 protein and the number of eosinophils (EG2), mast cells ftryptase), and T-lymphocytes (CD3) in the submucosa. Results As compared with controls, the number of eosinophils was increased to a similar degree in both asthma (P < 0.001) and in exacerbations of ehronic bronchitis (P < 0.001). whereas the number of I L-5 immunopositive cells was increased significantly only in asthma (P < 0.01). No diflerences were observed in the number of tnast cells and T-lymphocytes between the four groups of subjects examined. Conciusions This study shows that the degree of airway eosinophilia is similar in asthma and in exacerbations of ehronic bronchitis, but only in asthma is it associated with an increased expression of I L-5 protein in the bronchial tnucosa.     

Human MSH2 binds to trinucleotide repeat DNA structures associated with neurodegenerative diseases

The expansion of trinucleotide repeat sequences is associated with several neurodegenerative diseases. The mechanism of this expansion is unknown but may involve slipped-strand structures where adjacent rather than perfect complementary sequences of a trinucleotide repeat become paired. Here, we have studied the interaction of the human mismatch repair protein MSH2 with slipped-strand structures formed from a triplet repeat sequence in order to address the possible role of MSH2 in trinucleotide expansion. Genomic clones of the myotonic dystrophy locus containing disease-relevant lengths of (CTG)n x (CAG)n triplet repeats were examined. We have constructed two types of slipped-strand structures by annealing complementary strands of DNA containing: (i) equal numbers of trinucleotide repeats (homoduplex slipped structures or S-DNA) or (ii) different numbers of repeats (heteroduplex slipped intermediates or SI-DNA). SI-DNAs having an excess of either CTG or CAG repeats were structurally distinct and could be separated electrophoretically and studied individually. Using a band-shift assay, the MSH2 was shown to bind to both S-DNA and SI-DNA in a structure- specific manner. The affinity of MSH2 increased with the length of the repeat sequence. Furthermore, MSH2 bound preferentially to looped-out CAG repeat sequences, implicating a strand asymmetry in MSH2 recognition. Our results are consistent with the idea that MSH2 may participate in trinucleotide repeat expansion via its role in repair and/or recombination.      

Incomplete rescue of cystic fibrosis transmembrane conductance regulator deficient mice by the human CFTR cDNA

We have used a mouse model to study the ability of human CFTR to correct the defect in mice deficient of the endogenous protein. In this model, expression of the endogenous Cftr gene was disrupted and replaced with a human CFTR cDNA by a gene targeted 'knock-in' event. Animals homozygous for the gene replacement failed to show neither improved intestinal pathology nor survival when compared to mice completely lacking CFTR. RNA analyses showed that the human CFTR sequence was transcribed from the targeted allele in the respiratory and intestinal epithelial cells. Furthermore, in vivo potential difference measurements showed that basal CFTR chloride channel activity was present in the apical membranes of both nasal and rectal epithelial cells in all homozygous knock-in animals examined. Ussing chamber studies showed, however, that the cAMP-mediated chloride channel function was impaired in the intestinal tract among the majority of homozygous knock-in animals. Hence, failure to correct the intestinal pathology associated with loss of endogenous CFTR was related to inefficient functional expression of the human protein in mice. These results emphasize the need to understand the tissue- specific expression and regulation of CFTR function when animal models are used in gene therapy studies.