Short-term outcome and predictors of adverse events following pulmonary thromboendarterectomy

Pulmonary complications including hypoxemia, right heart failure, and prolonged ventilation may follow pulmonary thromboendarterectomy (PTE) performed via cardiopulmonary bypass (CPB) with deep hypothermic circulatory arrest. Seventeen adult patients have undergone PTE at the University of Maryland Medical System during the preceding 3 years. From these patients, clinical and hemodynamic parameters were tabulated pre-CPB, post-CPB, at admission to the intensive care unit (ICU), and prior to discontinuation of invasive monitoring in the ICU. Data on anthropometric variables, survival, and times of extracorporeal circulation, mechanical ventilation, and hospital stay were also collected. The mean values for pulmonary arterial systolic and diastolic pressures and pulmonary vascular resistance (PVR) decreased significantly from pre-CPB values after PTE (all p < 0.05). Mild mixed acidosis present at ICU admission resolved prior to discharge (p = 0.002). The length of mechanical ventilation time was positively correlated with the absolute post-CPB PVR and negatively correlated with the relative change in central venous pressure (CVP) from pre-CPB to post-CPB values (r = 0.75, p = 0.037). Of the pre-CPB anthropometric variables, only body mass index was significantly higher in nonsurvivors (p = 0.037). Pulmonary artery pressures and vascular resistance fall significantly after PTE. A lower post-CPB PVR and a relatively decreased (i.e., from pre-CPB values) CVP predict reduced length of postoperative ventilation but not of the hospital stay. Mortality appears increased in patients with a large body habitus.     

Cutting the costs of migraine: role of the employee health unit

It is estimated that over 120 million Americans suffer from moderate to severe attacks of migraine characterized by headache and other debilitating symptoms, resulting in impaired functional capacity and diminished quality of life. And, it appears, its prevalence is increasing. Since the prevalence peaks during the ages of 25-55, the prime working years, migraine places a tremendous burden on employers, primarily in the form of lost productivity as well as increased health benefits costs. The fact that migraine is underdiagnosed and undertreated suggests the existence of opportunities for interventions that will reduce that toll. This article focuses on the contributions that employee health units may make to such interventions. In addition to first aid for migraine attacks occurring during working hours, these interventions may include educating occupational health staff, managers, and line supervisors about the management of migraine; identifying migraineurs in the workforce; educating them about their problem and ensuring that they are receiving optimal care; controlling exposures to factors in the workplace that may trigger migraine attacks; and managing disability to minimize loss of productivity. Perhaps most important is encouraging migraineurs to be more aggressive in confronting this problem and empowering them to seek out personal physicians who will guide them to effective treatment and preventive regimens.     

A re-audit of pulmonary function laboratories in the West Midlands

In 1991 the West Midlands Pulmonary Function Audit Group examined the consistency between pulmonary function laboratories in the West Midlands. Three healthy subjects visited 22 centres and performed a standard set of pulmonary function tests. Demographic data on nine hypothetical subjects was also supplied for the laboratories to produce predicted values. Equipment was checked for accuracy using standard methods. The 1991 audit revealed significant inter-laboratory variability. Sources of error were identified and after consultation, recommendations were made to improve consistency. In addition, national and regional training workshops were organized for laboratory staff. In 1995 the audit was repeated using the same three subjects. Significant differences continued for all predicted results except for residual volume (RV) and forced vital capacity (FVC) and for all measured results except for functional residual capacity (FRC). However, improvements in the coefficient of variation were seen compared with 1991 for predicted forced expiratory volume (FEV1), total lung capacity (TLC), gas transfer (TLCO), FVC, FRC and RV. Similar improvements were seen in measured results for FEV1 and FVC. Increased variation was seen for predicted corrected transfer factor (KCO) and actual RV. The majority of variables in the 1995 audit had a coefficient of variation of less than 5% between laboratories. Analysis of the predicted results from the hypothetical subjects continued to show unacceptable variation reflecting continuing computer algorithm inconsistency. The improvements seen are encouraging and suggest that a regular audit programme is worthwhile.     

A magnetic evaluation of peripheral nerve regeneration: I. The discrepancy between magnetic and histologic data from the proximal segment

Histologic techniques can quantify the number of axons in a nerve, but give no information about electrical conductibility. The number of functional myelinated neuronal units in a nerve can be quantified based on a magnetic recording technique. When studying reconstructed peripheral nerves a significant difference between the results found with these two techniques can be observed. A comparison was made between the long-term changes in the number of histologically and magnetoneurophysiologically measured neuronal units proximal to a nerve reconstruction. This study was performed on 6 New Zealand White rabbits, 20 weeks after the peroneal nerve had been reconstructed. The contralateral nerves were used as a control. Histologic examination demonstrates a statistically significant decrease of approximately 5% in the number of myelinated fibers. The magnetoneurophysiological results demonstrate a decrease which is estimated to be caused by the loss of approximately 50% of the functional myelinated neuronal units in the nerve. Therefore we conclude that of the initially available myelinated neuronal units, 5% degenerate completely, 45% are vital but lose their signal conducting capability, and the remaining 50% are vital and continue to conduct signals. Apparently, only this latter group of 50% of the initially available functional neuronal units appears to remain available for functional recovery.     

Intracellular calcium regulates agrin-induced acetylcholine receptor clustering

Agrin is an extracellular matrix protein that directs neuromuscular junction formation. Early signal transduction events in agrin-mediated postsynaptic differentiation include activation of a receptor tyrosine kinase and phosphorylation of acetylcholine receptors (AChRs), but later steps in this pathway are unknown. Here, we have investigated the role of intracellular calcium in agrin-induced AChR clustering on cultured myotubes. Clamping intracellular calcium levels by loading with the fast chelator BAPTA inhibited agrin-induced AChR aggregation. In addition, preexisting AChR aggregates dispersed under these conditions, indicating that the maintenance of AChR clusters is similarly dependent on intracellular calcium fluxes. The decrease in AChR clusters in BAPTA-loaded cells was dose-dependent and reversible, and no change in the number or mobility of AChRs was observed. Clamping intracellular calcium did not block agrin-induced tyrosine phosphorylation of the AChR beta-subunit, indicating that intracellular calcium fluxes are likely to act downstream from or parallel to AChR phosphorylation. Finally, the targets of the intracellular calcium are likely to be close to the calcium source, since agrin-induced AChR clustering was unaffected in cells loaded with EGTA, a slower-binding calcium chelator. These findings distinguish a novel step in the signal transduction mechanism of agrin and raise the possibility that the pathways mediating agrin- and activity-driven changes in synaptic architecture could intersect at the level of intracellular calcium fluxes.     

Effects of ammonium dinitramide on preimplantation embryos in Sprague-Dawley rats

Ammonium dinitramide (ADN) is a class 1.1 oxidizer that may be used in rocket propellants and explosives. Previous studies have shown that ADN is a female reproductive toxicant, causing implantation failure in Sprague-Dawley rats when it is administered during the preimplantation period of gestation. The purpose of this follow-up study was to identify the mechanism(s) associated with implantation failure following exposure to ADN. Mated female rats were treated with 2.0 grams per liter (g l-1) ADN in their drinking water for 24, 48, 72, or 96 h before preimplantation embryos were harvested from the oviducts or uterine horns. On gestation day 1 (GD-1), comparable numbers of morphologically normal two-cell embryos were harvested from the oviducts of the treatment and control groups. On GD-2, the development of the embryos harvested from the treated animals was either slowed or halted when compared to the control embryos. By GD-4, 98% of the embryos harvested from the control group had developed to the morula or blastocyst stage; these were collected from the uterine horns. On GD-4 in the treated group, 41% of the harvested embryos remained at the two- to six-cell stage and 59% were degenerate; 82% of these embryos were collected from the oviducts. These data suggest that the implantation failure seen in animals treated with ADN is due to embryolethality.     

Banking: financing trends in an acquisitive health care market--focus on long-term care

This article reviews the long-term care sector of the health care industry, particularly the factors driving sector consolidation and, through the use of four transactions as a platform, discusses key credit issues and risks facing long-term care companies.     

TECHNICAL NOTE: measurement of cAMP-dependent protein kinase activity using a fluorescent-labeled kemptide

BACKGROUND: Traditional protein kinase assays include the use of [32P] labeled ATP as phosphate donor and a substrate protein or peptide as phosphoreceptor. Since this approach has a number of drawbacks in addition to generating ionizing radiation, several non-isotopic methods have been developed. Although shown to reflect the activity of purified enzymes, none have been demonstrated to detect physiological changes in endogenous enzyme activity in cell homogenates. METHODS: Studies were performed to examine the kinetics, reproducibility, and optimal assay conditions of a novel non-radioisotopic kinase assay that detects PKA activity by phosphorylation of the peptide substrate Kemptide covalently bound to a fluorescent molecule (f-Kemptide). Basal and agonist-induced PKA activity in epithelial cell homogenates was measured. RESULTS: The kinetics of f-Kemptide were similar to the standard radioisotopic method with intraassay and interassay variations of 5.6 +/- 0.8% and 14.3 +/- 2.6%, respectively. Neither fluorescence quenching nor enhancing effects were found with consistent amounts of homogenate protein. Specific PKA activity was determined as the IP20-inhibitable fraction to account for nonspecific phosphorylation, perhaps due to S6 kinase or a similar enzyme. The basal activity of 38% of total PKA in A6 cells increased by 84% after exposure to vasopressin and by 58% after short exposure to forskolin. In T84 cells exposed to VIP there was a 360% increase over basal activity. CONCLUSIONS: These results show that f-Kemptide exhibits acceptable kinetics, and that the assay system can quantitatively and reproducibly measure basal and stimulated PKA activity in cell homogenates.