Metabolic control and complications in Italian people with diabetes treated with continuous subcutaneous insulin infusion

Background and aim

The objective of this cross-sectional study was to evaluate the degree of glycaemic control and the frequency of diabetic complications in Italian people with diabetes who were treated with continuous subcutaneous insulin infusion (CSII).

Polymorphic and monomorphic HLA-DR determinants on human hematopoietic progenitor cells

The expression of monomorphic Ia-like antigens and polymorphic (allotypic) HLA-DR determinants on CFU-GM, BFU-E, CFU-E, and CFU-GEMM was studied in bone marrow and peripheral blood cells from normal healthy individuals. Using various polyclonal and monoclonal anti-Ia- like antibodies, the presence of HLA-DR backbone antigens was shown on all hematopoietic progenitor cells (HPC) studied, both in complement- dependent cytotoxicity assays and in fluorescence-activated cell sorting (FACS). The expression of allotypic determinants was demonstrated on all HPCs, using the HLA-DR typing sera anti-HLA-DR1, 2, 3, 4, 5, and 7. The Class II antigen MT-2 was also shown on all HPCs, using both monoclonal and alloantisera, whereas the MB-1 (DC-1) determinant could not be demonstrated on HPCs. This might open the possibility of removing MB-1-positive malignant cells from the graft in autologous bone marrow transplantation.     

Immunologic injury to vascular endothelial cells: effects on release of prostacyclin

Prostacyclin is released from cultured and ex vivo bovine vascular endothelium following sublethal immunologic injury by a heterologous antibody to endothelial cells developed in rabbits. This release was dependent on calcium and complement and was not enhanced by the presence of platelets. Prostacyclin release was diminished 1-2 hr after the injury, but recovered fully following reculture of the endothelial cells for 72 hr.     

Gamma (immune) interferon production by leukocytes from a patient with a TG cell proliferative disease

We report a patient with a disease characterized by proliferation of T cells with Fc receptors for IgG (TG). However, unlike lymphoid cells from normal individuals or from patients with other lymphoid malignancies, the patient's lymphocytes spontaneously produced gamma interferon (IFN-gamma) in vitro. The peripheral lymphocytes consisted of 95% TG cells, which exhibited the morphological characteristics of T- cell chronic lymphocytic leukemia (CLL) and were normal on cytochemical and chromosome analysis. The majority of TG cells were OKT3+, OKT8+, and OKT4-, 3A1-. These cells failed to express suppressor cell activity and displayed depressed levels of natural killer activity, but mediated antibody-dependent cell-mediated cytotoxicity. The spontaneous production of IFN-gamma by human peripheral lymphoid cells as demonstrated in this study may serve as a probe for studying the relationship between IFN-gamma and the proliferation of human T-cell subsets.     

Terminal deoxynucleotidyl transferase (TdT)-positive cells in cerebrospinal fluid and development of overt CNS leukemia: a 5-year follow-up study in 113 children with a TdT-positive leukemia or non- Hodgkin's lymphoma

We investigated whether an indirect nuclear terminal deoxynucleotidyl transferase (TdT) immunofluorescence (IF) assay on single cells present in the cerebrospinal fluid (CSF) is more effective than conventional cytomorphology for early detection or exclusion of (minimal) meningeal leukemic infiltration in patients with a TdT+ malignancy. During a 5- year follow-up study, 1,661 consecutive CSF samples from 113 children with a TdT+ acute lymphoblastic leukemia (ALL) (n = 100), a TdT+ acute nonlymphoblastic leukemia (ANLL) (n = 8), or a TdT+ non-Hodgkin's lymphoma (NHL) (n = 5) were analyzed. In 1,511 (91.9%) of 1,643 evaluable CSF samples, the positive and negative findings of both cytomorphology and the TdT-IF assay were concordant. In 47 (2.9%) samples from 28 patients, the cytomorphology was suspect while the TdT- IF assay was negative; follow-up as long as 58 months revealed no CNS leukemia in any patient. In 85 (5.2%) samples, cytomorphology was negative (n = 70) or suspect (n = 15) but TdT+ cells were detected. RBC contamination seriously hampered evaluation in 31 of these 85 samples. From the remaining 54 TdT+ samples from 29 patients, 40 samples preceded overt CNS leukemia in 20 patients. Two consecutive findings of TdT+ cells in the CSF were always followed by overt CNS leukemia. At initial diagnosis, 11 children had TdT+ cells in their RBC-free CSF. In one of these children, morphology was suspect; a repeated lumbar puncture was positive on both assays. Thus, initial CNS leukemia was diagnosed. In the other ten children, morphology was negative. In six of them, CNS leukemia was diagnosed 2 to 20 months later. In 32 other children examined at initial diagnosis, neither TdT+ cells nor blasts were observed in the CSF. In none of these patients was a CNS leukemia diagnosed after a follow-up of 2.5 to 57 months (median 24 months). In 207 control CSF samples from 58 children with TdT- oncologic, hematologic, or infectious diseases, no TdT+ cells could be detected. The TdT-IF assay is easy to perform and is a more reliable diagnostic tool for detection of CNS leukemia at an early stage than is cytomorphology. At initial diagnosis, the finding of Tdt+ cells in a RBC-free CSF sample with a negative cytomorphology is highly predictive for development of overt CNS leukemia.     

Preliminary evidence that etanercept may reduce radiographic progression in juvenile idiopathic arthritis

OBJECTIVE:To investigate the rate of radiographic progression, as measured with the carpo-metacarpal ratio (Poznanski score), during etanercept (ETN) therapy in children with polyarticular juvenile idiopathic arthritis (JIA). METHODS:Patients included in the Italian ETN registry who had a standard radiograph of both hands and wrists in the posteroanterior view made at start of treatment and after 1 year were included in the study. The clinical response was assessed by means of the ACR Pediatric definition of improvement. Radiographic progression was determined by calculating the change in the Poznanski score between the baseline and the 1-year radiographs.RESULTS:A total of 40 patients were studied. The frequency of ACR pediatric 30, 50, and 70 response at 1 year was 77%, 72%, and 50%, respectively. The median change in the Poznanski score between baseline and 1 year was + 0.3 units, meaning that, on average, patients experienced improvement in radiographic progression. CONCLUSION:Our pilot study provides evidence that ETN is potentially capable of reducing the progression of radiographic joint damage in JIA. This finding deserves confirmation in a controlled trial.     

Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts at diagnosis of childhood acute lymphoblastic leukemia: a pilot prognostic factor analysis

Lymphoblasts in bone marrow samples, obtained from 43 children with acute lymphoblastic leukemia at diagnosis, were incubated with 1.0 mumols/L [3H] methotrexate for 24 hours in vitro. Nonexchangeable methotrexate and methotrexate polyglutamates were separated and quantitated. Event-free survival at 5 years was 38% +/- 9% for all 43 patients (27 failures), and 44% +/- 10% for the 35 with non-T, non-B- cell acute lymphoblastic leukemia (20 failures). Of these 35 children, those whose lymphoblasts accumulated more than 100 pmol methotrexate and 500 pmol methotrexate polyglutamates per billion cells experienced better 5-year event-free survival than those whose lymphoblasts did not (65% +/- 12% v 22% +/- 9%, P = .010). This difference characterized "good-risk" patients who were female (P = .014), less than age 7 at diagnosis (P = .005), or had low initial white blood cell counts (less than 20 X 10(9)/L, P = .018). Findings were similar for the 43 children with acute lymphoblastic leukemia and for the "good-risk" children in this total group. Thus, the ability of lymphoblasts to accumulate methotrexate and form methotrexate polyglutamates may be important to the curative properties of current therapy of acute lymphoblastic leukemia in children, particularly for "good-risk" patients. In such patients, inherent rather than acquired drug resistance may be the initial event leading to treatment failure.     

Treatment of juvenile idiopathic arthritis with intra-articular triamcinolone hexacetonide: evaluation of clinical effectiveness correlated with circulating ANA and T gamma/delta + and B CD5+ lymphocyte populations of synovial fluid

OBJECTIVE: The aims of the study were to assess the effect of intra-articular treatment with triamcinolone hexacetonide (TH) in juvenile idiopathic arthritis (JIA) and to investigate whether treatment response correlates with the presence of antinuclear antibodies (ANA) in the serum and/or B CD5+ and T gamma/delta + lymphocytes in the synovial fluid. METHODS: A total of 37 patients (81% females, 56% ANA+) with oligoarticular JIA involving knees were treated with intra-articular injections of TH after failing to respond to NSAIDs for two months. Eighteen patients were treated within 6 months of onset, 19 were treated more than 6 months after onset. RESULT: Mean duration of remission was 13.9 months. Twelve patients (7 ANA+) had stable remission after a single injection; 13 patients (3 ANA+) experienced more than 6 months' remission but subsequently had a relapse; 12 patients (11 ANA+) had a relapse within six months of injection. Of 20 patients treated within 6 months of onset, 17 had stable remission whereas only 8 out of 17 who were treated during relapse attained stable remission (p = 0.03). The mean percentage of T gamma/delta + and of B CD5+ lymphocytes in synovial fluid was the same as in peripheral blood of normal subjects. CONCLUSION: Our data indicate that local treatment with slow-release steroids is very effective in oligoarticular JIA. Prolonged remission was less likely in the presence of ANA positivity, probably because the disease is immunologically more active. Finally, our data suggest that the earlier the treatment, the easier it is to obtain a protracted, and possibly permanent, response.