Hyperammonaemic encephalopathy after a subureteric injection for vesicoureteric reflux

A 6 year old boy developed hyperammonaemic encephalopathy following a subureteric injection for treatment of vesicoureteric reflux. The hyperammonaemia may be explained by a postoperative urinary tract infection with a urea splitting organism, leading to raised urine ammonia that was absorbed easily across a dilated urinary tract. Agitation and alteration in consciousness level following a urological procedure, in a child with a dilated urinary tract, may be signs of a treatable hyperammonaemic encephalopathy.     

Behavioural correlates of early-treated congenital hypothyroidism

Parents' and teachers' ratings were used to evaluate the behavioural characteristics of children with early-treated congenital hypothyroidism (CH). Comparisons were made between 63 children with early-treated CH and 34 healthy controls at the ages of 7.5 and 9.5 y. Additional comparisons were made between the two largest CH subgroups (thyroid agenesis, thyroid dysgenesis) and controls. The most marked differences were found on the introversion cluster and the motor clumsiness scale within it. Children with CH, particularly those with thyroid agenesis, showed introversion and motor clumsiness rather than social negativity and inattention. It is suggested that this behavioural profile may well have its origins in the often-reported inefficient motor behaviour of these children. Results are discussed in the light of recent findings suggesting an association between thyroid hormone problems and attention deficit hyperactivity disorder. Conclusion: Early-treated CH is associated with introversion rather than with social negativity.     

The CD4+ T lymphocyte is a site of steroid resistance in asthma

Phytohaemagglutinin (PHA)-induced T-cell proliferation is suppressed completely in steroid-sensitive asthma (SSA) by fluticasone propionate (FP). By contrast, in patients with steroid-resistant asthma (SRA), this proliferative response is only partially attenuated by steroids, which suggests that the T lymphocyte may harbour a key molecular defect in these patients. Both CD4+ and CD8+ T cells may be involved in orchestrating the inflammation underlying asthma. We examined whether CD4+ or CD8+ T cells isolated from SRA and SSA patients are equally susceptible to steroid suppression of PHA-induced proliferation. Complete suppression of CD4+ T-lymphocyte proliferation was seen in both SSA and control subjects at concentrations of 10(-9) M FP. In contrast, proliferation of CD4+ T cells from SRA patients was only partially inhibited, even at 10(-6) M FP. CD8+ responses from SRA, SSA and controls were all similar, with only a partial suppression of proliferation at 10(-6) M FP. Differential suppression by FP of CD4+ T cells has thus been demonstrated between SRA and SSA patients.      

Impact of anemia on clinical outcomes of patients with atrial fibrillation: The COOL‐AF registry

BackgroundTo determine whether anemia is an independent risk factor for ischemic stroke and major bleeding in patients with non‐valvular atrial fibrillation (NVAF).HypothesisAnemia in patients with NVAF increase risk of clinical complications related to atrial fibrillation.MethodsWe conducted a prospective multicenter registry of patients with NVAF in Thailand. Demographic data, medical history, comorbid conditions, laboratory data, and medications were collected and recorded, and patients were followed‐up every 6 months. The outcome measurements were ischemic stroke or transient ischemic attack (TIA), major bleeding, heart failure (HF), and death. All events were adjudicated by the study team. We analyzed whether anemia is a risk factor for clinical outcomes with and without adjusting for confounders.ResultsThere were a total of 1562 patients. The average age of subjects was 68.3 ± 11.5 years, and 57.7% were male. The mean hemoglobin level was 13.2 ± 1.8 g/dL. Anemia was demonstrated in 518 (33.16%) patients. The average follow‐up duration was 25.8 ± 10.5 months. The rate of ischemic stroke/TIA, major bleeding, HF, and death was 2.9%, 4.9%, 1.8%, 8.6%, and 9.2%, respectively. Anemia significantly increased the risk of these outcomes with a hazard ratio of 2.2, 3.2, 2.9, 1.9, and 2.8, respectively. Oral anticoagulants (OAC) was prescribed in 74.8%; warfarin accounts for 89.9% of OAC. After adjusting for potential confounders, anemia remained a significant predictor of major bleeding, heart failure, and death, but not for ischemic stroke/TIA.ConclusionAnemia was found to be an independent risk factor for major bleeding, heart failure, and death in patients with NVAF.     

Downregulation of the platelet surface glycoprotein Ib-IX complex in whole blood stimulated by thrombin, adenosine diphosphate, or an in vivo wound [see comments]

In washed platelet systems, thrombin has been demonstrated to downregulate the platelet surface expression of glycoprotein (GP) Ib and GPIX. In the present study, we addressed the question as to whether, in the more physiologic milieu of whole blood, downregulation of platelet surface GPIb and GPIX can be induced by thrombin, adenosine diphosphate (ADP), and/or by an in vivo wound. Thrombin-induced downregulation of GPIb and GPIX on the surface of individual platelets in whole blood was demonstrated by the use of flow cytometry, a panel of monoclonal antibodies (MoAbs) and, to inhibit fibrin polymerization, the peptide glycyl-L-prolyl-L-arginyl-L-proline. Platelets were identified in whole blood by a GPIV-specific MoAb and exclusion of monocytes by light scattering properties. Flow cytometric analysis of whole blood emerging from a standardized bleeding-time wound established that downregulation of platelet surface GPIb and GPIX can occur in vivo. A GPIb-IX complex-specific antibody indicated that the GPIb and GPIX remaining on the surface of platelets activated in vivo or in vitro were fully complexed. Simultaneous analysis of individual platelets by two fluorophores demonstrated that thrombin-induced platelet surface exposure of GMP-140 (degranulation) was nearly complete at the time that downregulation of platelet surface GPIb-IX was initiated. However, degranulation was not a prerequisite because ADP downregulated platelet surface GPIb-IX without exposing GMP-140 on the platelet surface. Inhibitory effects of cytochalasins demonstrated that the activation-induced downregulation of both GPIX and GPIb are dependent on actin polymerization. In summary, downregulation of the platelet surface GPIb-IX complex occurs in whole blood stimulated by thrombin, ADP, or an in vivo wound, and is independent of alpha granule secretion.     

Rivaroxaban vs. Warfarin in Japanese Patients With Atrial Fibrillation

Background:?The global ROCKET AF study evaluated once-daily rivaroxaban vs. warfarin for stroke and systemic embolism prevention in patients with atrial fibrillation (AF). A separate trial, J-ROCKET AF, compared the safety of a Japan-specific rivaroxaban dose with warfarin administered according to Japanese guidelines in Japanese patients with AF. Methods and Results:?J-ROCKET AF was a prospective, randomized, double-blind, phase III trial. Patients (n=1,280) with non-valvular AF at increased risk for stroke were randomized to receive 15mg once-daily rivaroxaban or warfarin dose-adjusted according to Japanese guidelines. The primary objective was to determine non-inferiority of rivaroxaban against warfarin for the principal safety outcome of major and non-major clinically relevant bleeding, in the on-treatment safety population. The primary efficacy endpoint was the composite of stroke and systemic embolism. Non-inferiority of rivaroxaban to warfarin was confirmed; the rate of the principal safety outcome was 18.04% per year in rivaroxaban-treated patients and 16.42% per year in warfarin-treated patients (hazard ratio [HR] 1.11; 95% confidence interval 0.87-1.42; P<0.001 [non-inferiority]). Intracranial hemorrhage rates were 0.8% with rivaroxaban and 1.6% with warfarin. There was a strong trend for a reduction in the rate of stroke/systemic embolism with rivaroxaban vs. warfarin (HR, 0.49; P=0.050). Conclusions:?J-ROCKET AF demonstrated the safety of a Japan-specific rivaroxaban dose and supports bridging the global ROCKET AF results into Japanese clinical practice. (Circ J?2012; 76: 2104-2111).     

Alterations of the p27KIP1 gene in non-Hodgkin's lymphomas and adult T- cell leukemia/lymphoma

The protein p27KIP1 belongs to a recently identified family of proteins termed cyclin-dependent kinase inhibitors (CDKIs). These proteins play an important role in regulating cell-cycle progression and loss of their function has been implicated in tumorigenesis. Transforming growth factor beta (TGF-beta) may induce cell growth arrest through p27 activation. TGF-beta often loses its ability to arrest growth of transformed cells; this could potentially occur through a defect in p27. To determine the role of p27 in tumorigenesis, we examined its mutational status in 74 non-Hodgkin's lymphomas (NHLs) (52 of B-cell phenotype, 22 of T-cell phenotype), 5 lymphoma cell lines, and 42 adult T-cell leukemias/lymphomas (ATLs) using polymerase chain reaction- single strand conformational polymorphism (PCR-SSCP) and Southern blot analyses. A nonsense mutation (stop codon) that could result in expression of a truncated nonfunctional p27 protein was detected at codon 76 in one case of acute lymphomatous ATL, but not in matched normal tissues. Previously undescribed polymorphisms were also identified at codon 109 in the lymphomas and at codon 55 in the ATLs. Two homozygous deletions of the p27 gene were detected in one case of B- immunoblastic NHL and in one case of acute ATL by Southern blot hybridization. These results indicate that p27 gene alterations are rare events in NHLs and ATLs, but may play an important role in the pathogenesis of some hematologic malignancies.     

Effects of purified bacterially synthesized murine multi-CSF (IL-3) on hematopoiesis in normal adult mice

Normal adult C57BL, BALB/c, and C3H/HeJ mice were injected intraperitoneally three times daily for up to 6 days with 102,000 U (200 ng) per injection of purified, bacterially synthesized, Multipotential colony-stimulating factor (CSF) (Interleukin-3) (rMulti- CSF) and compared with control mice injected with serum/saline with or without added endotoxin (1 ng/mL). Mice injected with rMulti-CSF exhibited tenfold rises in blood eosinophil and twofold to threefold rises in neutrophil and monocyte levels. The spleens from mice injected with rMulti-CSF showed a 50% increase in weight, elevated levels of maturing granulocytes, eosinophils, nucleated erythroid cells and megakaryocytes, and up to 100-fold rises in mast cells. Progenitor cell frequencies in the spleen were elevated sixfold to 18-fold. No significant changes were observed in the marrow. Sixfold to 15-fold rises were observed in peritoneal cell populations of mice injected with rMulti-CSF with evidence of increased peritoneal macrophage phagocytic activity. Livers of C57BL mice, but not of the other strains, exhibited increased numbers of infiltrating hematopoietic cells whereas rises in mast cell numbers were observed in the mesenteric lymph node, skin, and gut in BALB/c and C3H/HeJ mice. Endotoxin was excluded as being responsible for the observed changes except possibly those involving peritoneal macrophage phagocytic activity. The results indicate that the injection of normal mice with rMulti-CSF significantly stimulates the same types of hematopoietic populations as are stimulated in vitro by Multi-CSF and indicate that this and other CSFs should be useful in stimulating hematopoietic repopulation and functional activity in vivo.     

Unequal crossing-over: a common basis of single alpha-globin genes in Asians and American blacks with hemoglobin-H disease

The alpha-globin genes of five black Americans, two Chinese, and five Filipinos with HbH disease (an alpha-thalassemia state in which there is a single functional alpha gene) were analyzed by restriction endonuclease techniques. All subjects were found to have one chromosome 16, lacking both alpha genes, and another containing a single alpha gene (--/-alpha). Restriction endonuclease patterns of the DNA obtained from all 12 subjects were identical and compatible with unequal crossing-over as the mechanism of origin of the single alpha gene in these individuals.     

Purified colony-stimulating factors enhance the survival of human neutrophils and eosinophils in vitro: a rapid and sensitive microassay for colony-stimulating factors

The survival of purified human blood neutrophils and eosinophils was monitored using microwell cultures. Survival was enhanced in cultures containing human or murine colony-stimulating factors (CSFs). The survival of both cell types was enhanced by purified recombinant human granulocyte-macrophage CSF and partially purified preparations of the native molecule, CSF alpha. Neutrophil but not eosinophil survival was enhanced by murine granulocyte-CSF and its human analogue CSF beta. Eosinophil but not neutrophil survival was enhanced by murine eosinophil differentiation factor (eosinophil CSF). The mature cell survival provided an assay system for CSF that was 10(2) to 10(3) more sensitive than the standard assay of stimulation of colony formation in agar cultures and could be completed within 48 hours. These results demonstrated that CSF induced and enhanced survival of mature human neutrophils and eosinophils in vitro. Furthermore, the lineage specificity of purified murine CSFs was retained in their action on human cells.