Impact of regional anesthesia on outcomes of geriatric patients undergoing lower extremity revascularization: A propensity score-matched cohort study

Lower extremity revascularization (LER) for peripheral artery disease in elderly patients is associated with a high risk of perioperative morbidity and mortality. This study aimed to a conduct retrospective review and propensity score matching analysis to determine whether the use of regional anesthesia (RA) instead of general anesthesia (GA) in geriatric patients undergoing LER for peripheral artery disease results in improved short-term mortality and health outcomes. We reviewed medical records of 1271 patients aged >65 years who underwent LER at our center between May 1998 and February 2016. According to the anesthesia method, patients were grouped in the GA and RA groups. The primary outcome was short-term mortality (7-day and 30-day). The secondary outcomes were 5-year survival rate, intraoperative events, postoperative morbidity, and postoperative length of stay. A propensity score-matched cohort design was used to control for potentially confounding factors including patient demographics, comorbidities, American Society of Anesthesiologists physical status, and preoperative medications. After propensity score matching, 722 patients that received LER under GA (n = 269) or RA (n = 453) were identified. Patients from the GA group showed significantly higher 7-day mortality than those from the RA group (5.6% vs 2.7% P = .048); however, there was no significant difference in 30-day mortality between the groups (GA vs RA: 6.3% vs 3.6%, P = .083). The 5-year survival rate and incidence of arterial and central venous catheter placement or intraoperative dopamine and epinephrine use were significantly higher in the GA group than in the RA group (P < .05). In addition, the frequency of immediate postoperative oxygen therapy or mechanical ventilation support was higher in the GA group (P < .05). However, there was no difference in the postoperative cardiopulmonary and cerebral complications between the 2 groups. These results suggest that RA can reduce intraoperative hemodynamic support and provide immediate postoperative respiratory intensive care. In addition, the use of RA may be associated with better short-term and 5-year survival rates in geriatric patients undergoing LER.     

Purification of the 33,000-dalton ligand binding-protein constituent of the lymphoblast substance P receptor

Substance P (SP) acts as an immunoregulator by binding to specific functional cell surface receptors on a subpopulation of human T-helper lymphocytes. Receptors with similar properties have also been characterized on the human IM-9 B-lymphoblast cell line. Four distinct proteins of molecular weight (MW) 33,000, 58,000, 78,000, and 116,000 can be specifically affinity labeled using [125I]-SP Bolton-Hunter reagent and disuccinymidyl suberate (DSS). Peptide-mapping studies of these individually purified affinity labeled proteins have shown that the 33,000 MW membrane protein is present in the higher molecular weight cross-linked proteins. In the present studies, the 33,000 MW affinity-labeled protein was purified using semipreparative sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) followed by high-performance hydroxylapatite chromatography. Starting with 800 mg of affinity-labeled protein, the final yield was 39.0 micrograms of 33,000 MW affinity-labeled protein. Based on an estimate of 53 mg receptor per 800 mg membrane protein, this represents an overall yield of greater than 70%. Peptide mapping was done by digesting 20 micrograms of the receptor protein with bovine trypsin. The proteolytic fragments were separated by reverse-phase high-performance liquid chromatography, and the amino acid content of 13 distinct peptides was determined. With this procedure, sufficient receptor can now be purified so that partial amino acid sequences can be obtained for further structural studies.     

Agonistic activities of histamine-albumin conjugates at histamine H2 receptors on human HL-60 promyelocytic leukemia cells

We previously identified functional histamine H2 receptors on human HL-60 promyelocytic leukemia cells [J. Biol. Chem. 264: 18356-18362 (1989)]. In the present study, we have compared the action of histamine-albumin conjugates on H2 receptor activation with that of histamine alone. Both histamine and conjugates increased intracellular levels of Ca2+ in an H2 receptor-specific manner. However, binding of fluoresceinated histamine-albumin conjugates to HL-60 cells was not dissociated by 10(-4) M unlabeled histamine, although this concentration of histamine significantly desensitized conjugate responses. These data suggest that histamine-albumin conjugates not only activate H2 receptors but also bind to HL-60 cells nonspecifically or in an H2 receptor-unrelated manner. Moreover, histamine-induced Ca2+ mobilization was transient, whereas conjugate-induced Ca2+ mobilization was sustained for more than 10 min, as a result of the influx of extracellular Ca2+. Therefore, the functional difference between histamine and conjugates may provide a good model for the further understanding of the activation mechanisms of receptor-operated Ca2+ influx.     

Changes in urinary proximal tubule parameters in neonatal rats exposed to cadmium chloride during pregnancy.

Pregnant Sprague-Dawley rats were injected intraperitoneally with physiological saline solution (vehicle) or cadmium chloride (CdCl2) at 2.0 or 2.5 mg kg-1 on days 8, 10, 12 and 14 of gestation. On postnatal day (PND) 3, 12 or 49, the offspring were examined for 8- or 24-h urinary excretion of beta 2-microglobulin (beta 2-m), metallothionein (MT) and urinary activity of three proximal tubular enzymes: gammaglutamyl transferase (GGT), alkaline phosphatase (ALP) and N-acetyl-beta-glucosaminidase (NAG). Treatment with CdCl2 did not affect growth or survival of offspring. Significant decreases in the urinary excretion of GGT, ALP and NAG were observed on PND 3, at both doses. Exposure to 4 x 2.5 mg kg-1 resulted in functional deficit of the proximal tubule on PND 3, as evidenced by the significant increase in beta 2-m. Except for a slight but significant increase of beta 2-m in 49-day-old males, all the other urinary parameters returned to control values on PND 12. There was no effect on MT. Results from this study show that prenatal exposure to CdCl2 can induce significant changes in the kidney biochemistry of rats in the early postnatal period.     

Cobalt-induced epilepsy: an ultrastructural study

Metallic cobalt and aluminum rods were implanted into the cerebral cortices of rats. Almost all the animals with cobalt implantation were found to be epileptic 30 days after the operation. Tissue samples from the cerebral cortices were sampled for electron microscopy. The most significant changes in the cobalt-implanted animals were the disintegration of the rough endoplasmic reticulum in many cortical neurons and the accumulation of neurofilaments within the perikaryon. Such filamentous accumulation was usually found near the perinuclear position, at the periphery of the neurons, and in areas where there was a paucity of regular rough endoplasmic reticulum. Large aggregates of SER-like tubulovesicular structures were also found within many neuronal processes. Some of these neuronal processes could be identified to be postsynaptic dendritic terminals. Large nuclear pseudo-inclusions consisting of cytoplasmic materials were also found in some cortical neurons. These ultrastructural changes could also be occasionally observed in the opposite (cobalt-free) hemisphere of the brain (mirror image) in the cobalt-implanted animals. However, the brains of the aluminum-implanted or blank-control animals were free from any of these changes.     

Neuropathy in chronic obstructive pulmonary disease: a multicentre electrophysiological and clinical study.

The incidence and type of neuropathy in patients with chronic obstructive pulmonary disease (COPD) were assessed. In a selected group of 89 patients, abnormal nerve conduction studies were found in 44%. Electrophysiological signs of a generalized peripheral neuropathy were found in 5-18%, depending on diagnostic criteria. Lesions which were thought to be due to compression or other forms of trauma were present in a further 24%. In the patients with peripheral neuropathy, the changes were distally predominant, affected mainly sensory fibres, and were consistent with an axonal type of neuropathy. There was a significant correlation between age and the incidence of peripheral neuropathy. Electrophysiological evidence of neuropathy was three times as common as clinical evidence. Much of the variation in the reported incidence of neuropathy in COPD is probably due to imprecise diagnostic criteria.     

Representation of affinity in the case of co-operativity in protein-ligand binding

Summary— We have already proposed a "Global Association Function" to represent the global affinity of proteins to a drug; it was first applied in the case of independent binding sites. In this paper, we show that this same function can also be used to assess interactions between sites by varying the number of interacting sites and their co-operativity level. The resulting curves in two application cases are given together with the corresponding Scatchard plot: i) in a system with one single class of identical and interacting sites, ii) in a system with two classes of sites in which either primary or secondary are interacting; unexpectedly, in this latter case we also observed that sometimes positive co-operativity occasionally resulted in a concave-up Scatchard plot which is unusually admitted. In addition, as described in one example, our function is assumption free; this might be an advantage over usual methods, such as discrete parameter methods, because they require additional and empirical hypotheses on their related binding model.