Cognitive behavioral treatment for young children with obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a distressing and functionally impairing disorder that can emerge as early as age 4. Cognitive behavior therapy (CBT) for OCD in youth shows great promise for amelioration of symptoms and associated functional impairment. However, the empirical evidence base for the efficacy of CBT in youth has some significant limitations, particularly as related to treating the very young child with OCD. This report includes a quantitative review of existing child CBT studies to evaluate evidence for the efficacy of CBT for OCD. It identifies gaps in the literature that, when addressed, would enhance the understanding of effective treatment in pediatric OCD. Finally, it presents a proposed research agenda for addressing the unique concerns of the young child with OCD.     

Annexin A5 and the failing heart; lost or found in translation?

Heart failure is the number one reason for hospital admissionin patients above 65 years of age. It is predicted that thenumber of heart failure patients will almost double in the next20 years. Ischaemic and hypertensive heart disease are the majorcauses of this disabling disease. Approximately 22% of womenand 46% of men who have had a myocardial infarction will developheart failure within 6 years.¹ Still, hypertension is a chiefcause of cardiac failure: diastolic dysfunction accounts for>50% of all heart failure patients.² In the world we livein, an increasing number of people become at risk of developinghypertension heart     

Hip fractures: failure of fixation and outcome of salvage arthroplasty

Between 1999 and 2005, we treated 41 patients with a total hip arthroplasty for failed fixation of a hip fracture. This study had three purposes: (1) to determine the reason/s for fixation failure (2) to record difficulties/complications encountered in converting to a salvage arthroplasty and (3) to compare the outcome of these patients (Group 1) with a matched group of patients who underwent a primary hip arthroplasty (Group 2). Failure to achieve a good reduction and optimal screw placement was evident in 80% of cases of failed fixation. A high incidence of complications was recorded in the perioperative period during conversion to a salvage arthroplasty. Functional outcome was statistically inferior in Group1; this group also had a higher incidence of complications. Radiographs at 2 years postoperatively showed evidence of femoral stem loosening in 16% of the salvage group compared with 3% in the primary hip arthroplasty group.     

The effect of temporal adverbials on past tense production by children with specific language impairment.

PURPOSE: Children with specific language impairment (SLI) often fail to produce past tense forms in obligatory contexts, although the factors affecting such inconsistency are not well understood. This study examined the influence of accompanying temporal adverbials (e.g., just, already) on the past tense production of these children. METHOD: Fifteen preschool-aged children with SLI, 15 typically developing children matched for age (TD-A) and 15 younger typically developing children matched for mean length of utterance (TD-MLU) participated in the study. The children responded to probes that obligated the use of past tense forms. The verbal context provided by the experimenter for half of the items included a temporal adverbial. RESULTS: Overall, the SLI and TD-MLU groups produced past tense less frequently than the children in the TD-A group, and there were no significant differences between the SLI and the TD-MLU groups. However, both the SLI and the TD-MLU participants produced past tense forms less frequently when temporal adverbials were included than when they were absent. CONCLUSIONS: These findings suggest that the tendency to use past tense by the children with SLI and their younger MLU-matched peers may not have been independent of other types of temporal information.     

Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency.

Clinical and immunologic features of a recently recognized X-linked combined immunodeficiency disease (XCID) suggested that XCID and X-linked severe combined immunodeficiency (XSCID) might arise from different genetic defects. The recent discovery of mutations in the common gamma chain (gamma c) gene, a constituent of several cytokine receptors, in XSCID provided an opportunity to test directly whether a previously unrecognized mutation in this same gene was responsible for XCID. The status of X chromosome inactivation in blood leukocytes from obligate carriers of XCID was determined from the polymorphic, short tandem repeats (CAG), in the androgen receptor gene, which also contains a methylation-sensitive HpaII site. As in XSCID, X-chromosome inactivation in obligate carriers of XCID was nonrandom in T and B lymphocytes. In addition, X chromosome inactivation in PMNs was variable. Findings from this analysis prompted sequencing of the gamma c gene in this pedigree. A missense mutation in the region coding for the cytoplasmic portion of the gamma c gene was found in three affected males but not in a normal brother. Therefore, this point mutation in the gamma c gene leads to a less severe degree of deficiency in cellular and humoral immunity than that seen in XSCID.     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.     

Picotamide inhibition of excess in vitro thromboxane B2 release by colorectal mucosa in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. METHODS: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. RESULTS: Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147- 325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61- 140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64- 206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM). CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease.