Depletion of STAT5 blocks TEL-SYK-induced APMF-type leukemia with myelofibrosis and myelodysplasia in mice.

The spleen tyrosine kinase (SYK) was identified as an oncogenic driver in a broad spectrum of hematologic malignancies. The in vivo comparison of three SYK containing oncogenes, SYK(wt), TEL-SYK and IL-2-inducible T-cell kinase (ITK)-SYK revealed a general myeloexpansion and the establishment of three different hematologic (pre)diseases. SYK(wt) enhanced the myeloid and T-cell compartment, without leukemia/lymphoma development. ITK-SYK caused lethal T-cell lymphomas and the cytoplasmic TEL-SYK fusion induced an acute panmyelosis with myelofibrosis-type acute myeloid leukemia (AML) with up to 50% immature megakaryoblasts infiltrating bone marrow, spleen and liver, additional MPN features (myelofibrosis and granulocyte expansion) and MDS stigmata with megakaryocytic and erythroid dysplasia. LKS cells were reduced and all subsets (LT/ST/MPP) showed reduced proliferation rates. SYK inhibitor treatment (R788) of diseased TEL-SYK mice reduced leukocytosis, spleen and liver infiltration, enhanced the hematocrit and prolonged survival time, but could not significantly reduce myelofibrosis. Stat5 was identified as a major downstream mediator of TEL-SYK in vitro as well as in vivo. Consequently, targeted deletion of Stat5 in vivo completely abrogated TEL-SYK-induced AML and myelofibrosis development, proving Stat5 as a major driver of SYK-induced transformation. Our experiments highlight the important role of SYK in AML and myelofibrosis and prove SYK and STAT5 inhibitors as potent treatment options for those diseases.

Cognitive behavior therapy for depression in type 2 diabetes mellitus. A randomized, controlled trial.

BACKGROUND: Psychotherapy is the principal nonpharmacologic method for the management of depression, but its usefulness for depressed patients with diabetes remains unknown. OBJECTIVE: To assess the efficacy of cognitive behavior therapy (CBT) for depression in patients with diabetes. DESIGN: Randomized, controlled trial. SETTING: Referral-based academic medical center. PATIENTS: 51 patients with type 2 diabetes and major depression. INTERVENTION: Patients were assigned either to a group that received 10 weeks of individual CBT or to a control group that received no specific antidepressant treatment. All patients participated in a diabetes education program to control for the effects of supportive attention and the possible influence of enhanced diabetes control on mood. MEASUREMENTS: Degree of depression was measured by using the Beck Depression Inventory; glycemic control was measured by using glycosylated hemoglobin levels. Outcomes were assessed immediately after treatment and 6 months after treatment. RESULTS: The percentage of patients achieving remission of depression (Beck Depression Inventory score < or = 9) was greater in the CBT group than in the control group: posttreatment, 85.0% of patients in the CBT group (17 of 20) compared with 27.3% of controls (6 of 22) achieved remission (difference, 57.7 percentage points [95% CI, 33 to 82 percentage points]) (P < 0.001); at follow-up, 70.0% of patients in the CBT group (14 of 20) compared with 33.3% of controls (7 of 21) achieved remission (difference, 36.7 percentage points [CI, 9 to 65 percentage points]) (P = 0.03). Post-treatment glycosylated hemoglobin levels were not different in the two groups, but follow-up mean glycosylated hemoglobin levels were significantly better in the CBT group than in the control group (9.5% compared with 10.9%; P = 0.03). CONCLUSIONS: The combination of CBT and supportive diabetes education is an effective nonpharmacologic treatment for major depression in patients with type 2 diabetes. It may also be associated with improved glycemic control.

Altered patterns of posttransplant urinary tract infections associated with perioperative antibiotics and curtailed catheterization.

Postoperative urinary tract infections (UTIs) in renal transplant patients were studied before and after introduction of a protocol requiring single-dose perioperative antibiotics and earlier catheter removal. The overall incidence of UTIs was reduced from 55.4% to 26%. The most dramatic reduction was in nondiabetic males, from 56% to 8.2%. There was a small but statistically insignificant reduction in infection rates in females. There was no change in the rate of infection in diabetics. The incidences of noncoliform and mixed infections, in the group as a whole, were dramatically reduced from 42.9% to 12%, but Escherichia coli infections were totally unaffected. This protocol exposed the special susceptibility of women and diabetics to posttransplant UTIs and the different pathogenesis of E coli versus noncoliform infections. These features need more study.

Day treatment as an aid to mainstreaming troubled children.

Problem children who are diverted from public school programming into a private psychoeducational day facility in a community mental health center are followed up in a 10-year study to determine the rate of return to regular classes. The evidence points to a successful reintegration into public schools for the great majority of students. A philosophy for mainstreaming which supports the need for proper preparation of children for public school reentry is basic to effective management.

Children's services--past, present, future.

Preventing, healing, and educating in various forms have always been major ingredients of clinical services for troubled children. Traditional services involving healing or prevention have been emphasized. Current times mandate a closer look at the value of an educationally oriented model to provide direction for clinical intervention. Case illustrations of such a model are presented.

Parenting for foster parents.

A parenting course for foster parents was described with a follow-up evaluation utilized to determine its effectiveness. The content of this broad-based course included learning theory, principles and techniques, communication skills, methods of conflict resolution, developmental considerations, and information about community services. Results of the evaluation suggested that most of the participants had found the course helpful and were using the knowledge acquired.

A study in childhood egocentricity.

The SFSC was administered to 79 children and 63 adolescents who were considered to be functioning at a normal level. The ratio of self-focus to environment focus scores was related significantly to age, which confirms a hypothesis based upon Piaget's theory of mental development. Deviations from a relatively equal S/E ratio have been associated previously with psychopathology in adults. This was not found in the present study. It was suggested that an even S/E ratio may be inappropriate for children and youth, whose response styles are still in a state of development.