Sustained hypoxia depresses sensory processing of respiratory resistive loads

RATIONALE: The combination of acute hypoxia and increased respiratory load is encountered in several respiratory diseases including acute life-threatening asthma and sleep apnea. Hypoxia has been shown to inhibit respiratory load perception in healthy and asthmatic subjects, and could contribute to treatment delays and impaired function of protective reflexes. OBJECTIVES: Using respiratory-related evoked potentials (RREPs) this study aimed to determine the sensory processes mediating hypoxia-induced suppression of respiratory load sensation. METHODS: EEG was measured over the central and parietal cortical regions in 14 healthy subjects. RREPs were elicited by 500-ms midinspiratory resistive load stimuli during and after isocapnic normoxia or hypoxia (blood arterial O2 saturation approximately 80%). On a separate occasion, subjects rated the perceived magnitude of five externally applied inspiratory resistive loads (range, 8.6-43.7 cm H2O x L(-1) x s) under similar experimental conditions. In both experiments subjects voluntarily ventilated approximately 90% above baseline to match ventilatory output between gas conditions. RESULTS: RREP stimulus was matched between gas conditions in 11 subjects (minimum mask pressure -9.7 +/- 0.6 versus -9.2 +/- 0.4 cm H2O). P1 and P2 amplitudes were reduced during isocapnic hypoxia compared with normoxia (maximal at Cz: P1, 2.5 +/- 1.1 versus 3.9 +/- 1.2 microv, p = 0.03; P2, 10.0 +/- 2.2 versus 12.4 +/- 2.1 microv, p < 0.01, respectively). Perceived magnitude of externally applied resistive loads was also reduced during hypoxia compared with normoxia (17.1 +/- 1.1 versus 19.0 +/- 1.1 au, p < 0.01). CONCLUSIONS: These data confirm that isocapnic hypoxia suppresses respiratory load sensation. Decreased amplitude of the earlier (P1) RREP component suggests that this is mediated, at least in part, by suppression of respiratory afferent information before its arrival at the primary sensory cortex.     

Clonal evolution in atypical chronic granulocytic leukemia: a non- Philadelphia translocation

Hemopoietic cells in chronic granulocytic leukemia (CGL) frequently contain a chromosome translocation involving chromosome 22 and another autosome, usually number 9. The translocated chromosome 22 is known as the Philadelphia (Ph) chromosome. The appearance of a second Ph chromosome is the most common cytogenetic abnormality in CGL signaling the blastic phase. For 6 yr we serially studied a man with atypical CGL whose marrow cells were marked by a translocation from chromosome 18 to chromosome 11 [46XY,t(11;18)(q23;q12)]. Three months prior to blast transformation there appeared an extra copy of the marker chromosome 18: 47XY,t(11;18)(q23;q12),+(18p11 leads to 18q12). This man presents a new cytogenetic pattern of clonal evolution in CGL. The pattern is analogous to that of the Ph chromosome and is characterized by a balanced chromosomal rearrangement and the subsequent acquisition of an extra copy of the small translocation chromosome immediately prior to blast transformation.     

Functional interleukin-2 receptors are expressed on natural killer-like leukemic cells from a dog with cutaneous lymphoma

We identified a dog with large granular lymphocytic leukemia and cutaneous lymphoma that exhibited constitutive expression of interleukin-2 (IL-2) receptors by the leukemic peripheral blood lymphocytes. The leukemic cells phenotypically resembled natural killer (NK) cells, and their surface IL-2 receptors were functional, as determined by the capacity to bind human recombinant IL-2 with high- affinity resulting in the transduction of proliferation signals and in the development of lymphokine-activated killer cell activity. These cells produced IL-2 spontaneously, and they may have maintained their proliferative state through an IL-2-dependent autocrine growth pathway. Our results indicate that neoplastic lymphocytes of syndromes that involve circulating leukemic cells with dermotropism can originate from NK-like cells. Additionally, the data also suggest that proliferative conditions such as these may be the result of the aberrant production of IL-2. Further, this case illustrates the potential for the use of hematopoietic malignancies in the dog as a suitable animal model for immune targeting of IL-2 receptors as a novel treatment approach for similar malignancies of human beings.     

Persistence of Staphylococcus aureus as detected by polymerase chain reaction in the synovial fluid of a patient with septic arthritis

Septic arthritis commonly occurs in the rheumatoid arthritis population. The diagnosis is frequently delayed and the associated mortality is high. In this brief report, we present a patient with rheumatoid arthritis and prosthetic knee joints who developed septic arthritis and had persisting evidence of Staphylococcus aureus DNA in synovial fluid, from his knees, which was detected by polymerase chain reaction (PCR) and a gene probe. This was detected until 10 weeks of therapy despite adequate antibiotic treatment and a sterile synovial fluid. In the future, it may be found that PCR of the synovial fluid will be a valuable investigation for the diagnosis and management of septic arthritis.      

Normalization of markers of coagulation activation with a purified protein C concentrate in adults with homozygous protein C deficiency

Homozygous or double heterozygous protein-C deficiency can present at birth with purpura fulminans or later in life with venous thrombosis. Two homozygous patients who had previously sustained thrombotic episodes were investigated at a time when they were asymptomatic and not receiving antithrombotic therapy. The plasma levels of protein-C antigen and activity in both individuals were approximately 20% of normal. We administered a highly purified plasma-derived protein C concentrate to these individuals and monitored levels of several markers of in vivo coagulation activation. Assays for protein-C activation (activated protein C and protein C activation peptide) showed a sustained increase from reduced baseline levels, whereas thrombin generation (as measured by prothrombin fragment F1 + 2) gradually decreased over about 24 hours into the normal range. These investigations provide direct evidence that protein C is converted to activated protein C in vivo, and that the protein-C anticoagulant pathway is a tonically active mechanism in the regulation of hemostatic system activation in humans.     

Reducing Sodium Intake in Children: A Public Health Investment

The antecedents of elevated blood pressure (BP) and its major consequences (cardiovascular disease and stroke) begin in childhood. Higher levels of BP early in life track into adulthood and are associated with subclinical target organ damage in children and adults. Diet behaviors, including the choice of high sodium containing foods, are established during childhood. On average, children, ages 2‐19, consume more than 3,100 mg of sodium per day, with substantially greater sodium intakes in boys than girls. Importantly, studies show that lowering sodium intake in children lowers blood pressure. In view of this evidence, US Dietary Guidelines recommend a reduced sodium intake in children. Current federal nutrition standards include a step‐wise reduction in the sodium levels of school meals. The ultimate goal is to help children achieve daily sodium intakes that do not exceed upper levels recommended by the Institute of Medicine and the Dietary Guidelines for Americans. In summary, available data are sufficiently strong to recommend a lower sodium intake beginning in early in life as an effective and well‐tolerated approach to reducing BP in children. Current efforts to weaken nutrition standards for school meals undermine an effective strategy aimed at improving the health of our children and our nation.     

Multiphasic presentation of Rasmussen's encephalitis

Rasmussen's encephalitis is a rare, chronic inflammatory disorder of unknown cause, characterised by drug‐resistant focal epilepsy that may rarely present in adolescence or adulthood. We present a case of Rasmussen's encephalitis with prominent recurrent fluctuation in symptoms and well‐documented fluctuating changes on MRI, adding to the spectrum of diversity of Rasmussen's encephalitis.