Granulocyte-macrophage colony-stimulating factor preferentially activates the 94-kD STAT5A and an 80-kD STAT5A isoform in human peripheral blood monocytes.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces immediate effects in monocytes by activation of the Janus kinase (JAK2) and STAT transcription factor (STAT5) pathway. Recent studies have identified homologues of STAT5, STAT5A, and STAT5B, as well as lower molecular weight variants of STAT5. To define the activation of the STAT5 homologues and lower molecular weight variant in human monocytes and monocytes differentiated into macrophages by culture in macrophage-CSF (M-CSF), we measured the GM-CSF induced tyrosine phosphorylation of STAT5A, STAT5B, and any lower molecular weight STAT5 isoforms. Freshly isolated monocytes expressed 94-kD STAT5A, 92-kD STAT5B, and an 80-kD STAT5A molecule. Whereas 94-kD STAT5A was clearly tyrosine phosphorylated and bound to the enhancer element, the gamma response region (GRR), of the Fc gamma RI gene, substantially less tyrosine phosphorylated STAT5B bound to the immobilized GRR element. Macrophages lost their ability to express the 80-kD STAT5A protein, but retained their ability to activate STAT5A. STAT5A-STAT5A homodimers and STAT5A-STAT5B heterodimers formed in response to GM-CSF. Therefore, activation of STAT5A predominates compared to STAT5B when assayed by direct immunoprecipitation and by evaluation of bound STATs to immobilized GRR. Selective activation of STAT5 homologues in addition to generation of lower molecular isoforms may provide specificity and control to genes expressed in response to cytokines such as GM-CSF.

Detection of HIV-1 provirus in bronchoalveolar lavage cells by polymerase chain reaction.

This study was undertaken to evaluate whether HIV-seropositive individuals harbor HIV provirus in cells obtained by bronchoalveolar lavage (BAL). BAL cells were obtained from 14 HIV-positive patients undergoing bronchoscopy for evaluation of acute pulmonary symptoms. Cells were fractionated into macrophage-enriched and lymphocyte-enriched populations. The quantity of HIV-1 proviral DNA in the unfractionated BAL cells and in each population of fractionated cells was determined following polymerase chain reaction (PCR) amplification. Detectable quantities (3-90 copies/100,000 cells) of HIV-1 proviral DNA were found in unfractionated BAL cells in 12 of 14 patients. In the other two patients, provirus was detected after a sevenfold enrichment of lymphocytes. Provirus was also detected in BAL macrophages from 8/14 patients although proviral content was significantly higher in the lymphocyte fraction (133 +/- 72 vs. 35 +/- 22 proviral copies, p = 0.03). No correlation was seen with the ability to detect provirus in lymphocyte- or macrophage-enriched fractions and clinical diagnosis (e.g., Pneumocystis carinii pneumonia). The data suggest that lymphocytes are the predominant cells that contain provirus found in the lungs, although macrophages may be infected in some patients.

Using a database to analyze core basic science content in a problem-based curriculum.

As medical schools critically reevaluate their methods of instruction and as the number of innovative programs increases, the content delivered across disciplines must be carefully reviewed. However, few methods of content analysis have been applied to problem-based programs. In 1989-90 and 1990-91, the authors analyzed the distribution of basic science content in the 53 cases in the problem-based curriculum of Rush Medical College of Rush University. They developed a content vocabulary and created a database using a widely available computer software program. The content areas specific to each case were identified by faculty using the content vocabulary. To determine whether these content areas were actually identified by the students participating in the problem-solving sessions, the authors surveyed the 36 student participants in the classes of 1993 and 1994 and also interviewed the 15 faculty facilitators of the sessions. The surveys and interviews demonstrated that over 90% of the content areas identified by the faculty were actually covered by the students. The authors conclude that the database assists in their review of the curriculum for omission and redundancy. Other uses and limitations of this method are also discussed.

The noninvasive respiratory care unit. Patterns of use and financial implications.

Clinical, socioeconomic, and ethical dilemmas have prompted reevaluation of traditional methods of providing intensive care. Six years ago, we established a noninvasive respiratory care unit (NRCU) for selected patients in need of intensive respiratory monitoring and therapy, particularly those requiring prolonged mechanical ventilation. One impetus for the formation of the NRCU was the expectation that it might prove to be a less costly alternative to the intensive care unit (ICU) for selected patients. We reviewed data from all patients admitted to the NRCU from July 1, 1987 through June 30, 1988 to identify characteristics of the patient population and to evaluate potential cost savings. During one year of operation, 136 patients were admitted to the unit, 107 of whom were mechanically ventilated. Overall, hospital costs for these patients exceeded payments by $1,519,477. Losses were greatest for mechanically ventilated patients and those for whom Medicare or Medicaid were the primary payors. Daily costs of care for mechanically ventilated patients were $1,976 lower in the NRCU than in the medical intensive care unit (MICU). We conclude that the NRCU represents a cost-effective approach to the care of substantial numbers of patients requiring specialized respiratory care.

Financial implications of ventilator care.

Mechanical ventilation is in the forefront of modern technologic advances. These advances can be life saving for some, death prolonging for others. As difficult medical, ethical, and economic issues are raised in relation to life-sustaining treatments, it is important to have as complete a data base as possible concerning costs and outcomes of mechanical ventilation, so that physicians, patients, families, and society as a whole can make appropriate decisions regarding its use.

Treatment of acute exacerbations in chronic obstructive pulmonary disease.

Therapeutic interventions introduced and refined over the last 10 years, including chronic home oxygen and improved bronchodilators, have resulted in more patients with chronic obstructive pulmonary disease living longer despite more severe functional abnormalities. Episodes of acute respiratory failure in this population remain a major complication requiring rapid assessment and intervention. This article focuses on the diagnostic approach and therapeutic interventions in the patient with obstructive lung disease who presents in acute respiratory distress.

Long-term outcomes for elderly survivors of prolonged ventilator assistance.

Care of ventilator-dependent patients requires considerable resources, yet the long-term outcomes of this type of care have rarely been described. We retrospectively investigated the posthospital course of elderly patients who survived an episode of prolonged ventilator dependency to describe survival rates, subsequent use of health care resources, and functional abilities. Our data suggest that the use of prolonged mechanical ventilation in the elderly produces few survivors at considerable expense. Poor overall outcomes occurred despite considerable consumption of medical and nursing resources by the survivors.

DRG payment for long-term ventilator patients--revisited.

This article provides a follow-up to an evaluation originally presented in Chest of the financial impact of diagnosis related group (DRG) payment for long-term ventilator-dependent Medicare patients at Rush-Presbyterian-St. Luke's Medical Center. Since the results of our original study were presented, the Health Care Financing Administration (HCFA) has created two new DRGs for patients who have respiratory principal diagnoses to help recognize the resource intensiveness associated with mechanical ventilator support. The original 95 patients' payment, which was originally calculated to be $2.2 million below costs, was recalculated to be $1.9 million below costs, representing a 13 percent reduction in the loss. We conclude that although HCFA's recent remedial action is a step in the right direction, it provides little relief from the DRG system's financial bias against long-term ventilator-dependent patients, because the new ventilator DRGs encompass only a small segment of these patients. As an alternative approach, we recommend a single DRG for patients who, regardless of their principal diagnoses, experience chronic respiratory failure requiring a minimum of three days of continuous ventilator treatment.

Economics of mechanical ventilation.

Mechanical ventilation is a life-saving medical advance. It has allowed many patients who previously would have died as a result of acute respiratory failure to survive. It has also created a population of patients who are unable to recover completely from their acute illness and who require prolonged mechanical ventilator support. The care for these patients raises many ethical, legal, social, economic, and medical issues. Data are needed to adequately meet the challenges of the ventilator-dependent patients in the future.

DRG payment for long-term ventilator patients. Implications and recommendations.

Much concern has been expressed about the Medicare Prospective Payment System's impact on access to care. In this study, we examine the financial impact of diagnosis-related group (DRG) payment for chronic ventilator-dependent Medicare patients. During a one-year period, payment for 95 Medicare patients who received a minimum of three days of continuous ventilator treatment and who spent no time in surgical intensive care at Rush-Presbyterian-St. Luke's Medical Center, was calculated to be $2.2 million below costs, representing an average loss per discharge of $23,129. Patients stayed an average of 26.6 days, of which 14.2 days were spent on a ventilator. We conclude that the results suggest a financial bias against chronic ventilator-dependent patients exists in the DRG system which could present access problems. We recommend three approaches to recognizing the cost of care for such patients in the DRG payment system and encourage those in public policy-making positions to use our results as the basis for a larger scale analysis of the impact of Medicare DRG payment on chronic ventilator-dependent patients.

Acute respiratory failure and chronic obstructive lung disease.

Patients with COPD who develop acute respiratory failure require special attention in their management. Patients with severe COPD often have cor pulmonale, complex acid/base compensations, and altered respiratory control mechanisms. These need to be considered when approaching the patient with an acute decompensation. Because of the improving prognosis in this group of patients, aggressive management should be undertaken using combinations of bronchodilator medications, oxygen, bronchial hygiene, and antibiotics.

Heparin and warfarin: use of anticoagulants in the prevention and treatment of venous thrombosis and pulmonary embolism.

The physician frequently encounters the problems of deep vein thrombosis and pulmonary embolism. Recently, a number of studies have been published which are of considerable help in the management of these disorders. It has been shown that in many cases, low-dose heparin is effective in the prevention of both venous thrombosis and pulmonary embolism. However, once venous thrombosis has already occurred, it is necessary to use full-dose heparin, preferably by the continuous intravenous route, with maintenance of the partial thromboplastin time (PTT) at 1 1/2 times the control at all times. Although monitoring the PTT may not prevent hemorrhage, it will help prevent further thrombosis. Heparin is generally continued for seven to ten days. During this time warfarin is generally begun, and it is important to continue the patient on warfarin for five to seven days while the patient is receiving intravenous heparin therapy. After stopping heparin, oral anticoagulation with warfarin should be continued for six weeks. Then, in the absence of a previous history of venous thromboembolism or a known predisposing condition, it is safe to abruptly discontinue anticoagulation in most patients.

Prevention of fatal pulmonary thromboembolism by heparin prophylaxis after surgery for hip fractures.

From 1960 through 1975, 337 patients with surgically treated acute fracture of the hip received subcutaneously administered heparin to prevent thromboembolic disease according to various regimens. Four hundred and three patients received no heparin. The incidence of fatal pulmonary embolism was 3.5 per cent in the 403 patients who reveived no heparin and 0.0 per cent in the 147 patients who were treated by the currently used regimen of prophylaxis, as follows: With the dose modified according to the coagulometer-test time, patients received 2,500 units on admission and every six hours until the day before operation. Then they were given 5,000 to 10,000 units eight to ten hours before surgery and 2,500 units every six hours after surgery until they were fully mobilized.