Obstructive sleep apnea, continuous positive airway pressure, and surgery

Patients with obstructive sleep apnea (OSA) who have undergone upper airway surgery could be expected to improve if surgery alleviated some or all of the anatomic obstructions, or continue to desaturate at preoperative levels if the surgery was not corrective. Factors such as morbid obesity, general anesthesia recovery, and operative edema can potentially cause desaturations below preoperative levels. Because of this risk, patients with severe OSA have been considered for protective tracheostomy. The findings of our study suggest that selected patients who would have been past candidates for protective tracheostomy while undergoing surgery for severe OSA can, as an alternative, be considered for immediate postoperative use of nasal continuous positive airway pressure (CPAP). Ten surgical patients with severe OSA who elected surgical treatment were successfully treated with CPAP immediately after extubation and postoperatively to assist with airway patency and hemoglobin saturation. Postoperative followup included monitoring of continuous pulse oximetry, cardiac activity, and intermittent arterial blood gases. Preoperatively, all ten patients had marked decrease in oxygen desaturation levels during sleep, with a mean nadir oxygen saturation (SaO2) to 51.5%. After surgery, all patients in this group maintained SaO2 levels to no lower than 90%, with a mean SaO2 level of 93% while using CPAP on room air (F10(2) 21%) only.     

Analysis of the plasminogen activator activity of the human glomerulus

An assay was developed to measure plasminogen activator activity from isolated human glomeruli. Activator was extracted from individual glomeruli with 0.2 M phosphate-buffered saline, pH 7.4 (PBS), containing 0.01% Triton X-100 and quantitated in 125I-fibrin films. Quenching studies using antibodies to tissue plasminogen activator and urokinase revealed that the extracted glomerular plasminogen activator activity contained both tissue plasminogen activator of urokinase. Monoclonal and polyclonal antibodies raised to tissue plasminogen activator demonstrated low-level inhibition of urokinase activity and monoclonal and polyclonal antibodies to urokinase demonstrated low-level inhibition of tissue plasminogen activator activity. The assay should be applicable to the study of glomerular plasminogen activator activity in experimental and human kidney diseases. The detection of antibody cross-reactivity to tissue plasminogen activator and urokinase may be related to the sensitivity of the 125I-fibrin assay and to the structural similarities of these activators.     

Detection of Mycobacterium leprae in ocular tissues by histopathology and real-time polymerase chain reaction

AIM: To report detection of leprosy in ocular tissue by histopathology and its confirmation by genetic analysis. METHODS: Excised tissue from a clinically-suspected ocular leprosy patient was processed and analyzed histopathologically. The DNA from the paraffin-embedded tissue was extracted, an 85 A-C intergenic region of Mycobacterium leprae was amplified using specific primers and analyzed by conventional as well as real-time polymerase chain reaction (RT-PCR). RESULTS: With periodic acid-Schiff-hematoxylin (PAS-H) staining the specimen showed presence of a thin fibrinous layer of inflammatory cells. The majority of the tissue was fibrovascular with extensive infiltration by histiocytes having reticulated cytoplasm. Modified PAS-H and acid-fast staining (AFS) showed the presence of several acid-fast organisms within the cytoplasm of histiocytes and mast cells. Conventional PCR showed a 250-bp DNA from excised conjunctival tissue, which was in agreement with the positive controls for M. leprae. Through RT-PCR, it was calculated that the suspected tissue had 44.68 pg of M. leprae DNA, which is 8937.06 genome copies of M. leprae. CONCLUSIONS: Presence of inflammatory cells and AFS bacilli in tissue presented a typical picture of leprosy. M. leprae DNA can be detected using RT-PCR in ocular tissues when acid-fast bacteria are seen in histopathological sections. And when the diagnosis of leprosy is inconclusive and acid-fast bacteria are seen, RT-PCR for M. leprae DNA could be used as a rapid confirmatory test to identify the presence of M. leprae and, therefore, the diagnosis of leprosy.     

Relationship of the clinical response and binding of recombinant interferon alpha in patients with lymphoproliferative diseases

Patients with hairy cell leukemia (HCL) and chronic lymphocytic leukemia (CLL) were treated with recombinant interferon alpha A (rIFN- alpha A). The binding of iodinated recombinant interferon-alpha to baseline samples of peripheral blood mononuclear cells (PBMCs) from the leukemia patients was compared with clinical responsiveness to rIFN- alpha A. HCL patients (8/10) responded to rIFN-alpha A therapy, whereas none (0/10) of the CLL patients studied responded. The PBMCs from the eight responsive HCL patients bound approximately twice as much iodinated interferon as the PBMCs from nonresponsive CLL patients. This difference was due to more high-affinity receptors per cell with no difference in the affinity of the interferon-receptor interaction. However, because PBMCs from HCL patients were larger than PBMCs from CLL patients, the cell surface receptor density was similar. The leukemic cells from one of the two nonresponsive HCL patients bound iodinated interferon similarly to the cells from the responsive HCL patients, whereas the leukemic cells from the other nonresponsive HCL patient bound considerably less. The rapidity of response of the HCL patients did not correlate with the level of binding of iodinated interferon. Our results suggest that the absolute number of interferon receptors per cell may be only one of several important parameters in the response to rIFN-alpha A therapy, and that the responsiveness of a particular lymphoproliferative disease or a particular patient to rIFN- alpha A therapy cannot be predicted or explained solely by the degree of interaction between IFN and its cell surface receptor.     

Interleukin-4 enhances the survival of severe combined immunodeficient mice engrafted with human B-cell precursor leukemia

Human interleukin-4 (huIL-4) has been shown to inhibit the growth in vitro of cells from patients with acute lymphoblastic leukemia (ALL). With the aim of determining whether this cytokine might be useful in the treatment of patients with ALL, the effects of huIL-4 on human B- cell precursor ALL engrafted in severe combined immunodeficient (SCID) mice were examined. The inhibition of [3H] thymidine uptake of primary ALL cells by huIL-4 was maintained following engraftment and passage of leukemia in SCID mice. Five of seven xenograft leukemias showed significant inhibition in vitro by huIL-4 at concentrations as low as 0.5 ng/mL; furthermore, huIL-4 counteracted the proliferative effects of IL-7. When used to treat two human leukemias engrafted in SCID mice, huIL-4 200 microgram/kg/d, as a continuous 14-day subcutaneous infusion, suppressed the appearance of circulating lymphoblasts and extended survival of mice by 39% and 108%, respectively, the first demonstration of IL-4 activity against human leukemia in vivo. The mean steady-state huIL-4 level in mouse plasma during the infusion was 1.46 ng/mL (SEM +/- 0.14 ng/mL), which was similar to concentrations found to be effective in vitro. ALL cells obtained from mice relapsing after huIL-4 treatment continued to show inhibition by the cytokine in vitro. These data suggest that IL-4 may be useful in the treatment of patients with ALL.