Acute respiratory distress syndrome due to pulmonary involvement by neoplastic plasma cells in multiple myeloma.

Pulmonary involvement with multiple myeloma occurs infrequently and may be difficult to distinguish from more common primary lung tumours, metastatic disease, or other pleural and parenchymal abnormalities. A patient who developed acute respiratory distress syndrome (ARDS) was subsequently found to have multiple myeloma with involvement of lung parenchyma by neoplastic plasma cells. Only one other report of ARDS in association with multiple myeloma was found, and there are no previous reports where the appearance of ARDS antedated a diagnosis of multiple myeloma. In patients with ARDS, parenchymal involvement from multiple myeloma should be included in the differential diagnosis.

The relationship between the angle of the tibial tunnel in the coronal plane and loss of flexion and anterior laxity after anterior cruciate ligament reconstruction.

Tension in an anterior cruciate ligament graft is greater with the knee in flexion when the angle of the tibial tunnel in the coronal plane is vertical or more perpendicular to the medial joint line of the tibia; however, the relationship of the angle of the tibial tunnel to knee function has not been studied. Greater graft tension may limit knee flexion or stretch the graft and increase anterior laxity. Five surgeons treated 119 subjects by reconstructing a torn anterior cruciate ligament using a double-looped semitendinosus and gracilis graft and a standardized technique. The femoral tunnel was drilled through the tibial tunnel. Radiographs were analyzed for tibial tunnel placement and a clinical evaluation was made 4 months postoperatively. Knees were assigned to subgroups according to the angle of the tibial tunnel in the coronal plane (65 degrees to 69 degrees, 70 degrees to 74 degrees, 75 degrees to 79 degrees, 80 degrees to 84 degrees, and 85 degrees to 89 degrees), with the angle of the latter subgroup being most vertical. Loss of flexion increased significantly from 0.5 degrees to 6.5 degrees and anterior laxity increased significantly from 0.5 to 2.2 mm as the tunnel angle was increased. The average angle of the tibial tunnel varied significantly, 11 degrees between surgeons (range, 69 degrees to 80 degrees). We found a tibial tunnel angle of 75 degrees or more is associated with greater loss of flexion and anterior laxity. Surgeons do not drill the angle of the tibial tunnel in the coronal plane accurately. We now routinely drill the tibial tunnel at an angle of 65 degrees to 70 degrees in the coronal plane because it may reduce loss of flexion and anterior laxity.

Documenting and comparing medical students' clinical experiences.

CONTEXT: The decentralization of clinical teaching networks over the past decade calls for a systematic way to record the case-mix of patients, the severity of diseases, and the diagnostic procedures that medical students encounter in clinical clerkships. OBJECTIVE: To demonstrate a system that documents medical students' clinical experiences across clerkships. DESIGN AND SETTINGS: Evaluation of a method for recording student-patient clinical encounters using a pocket-sized computer-read patient encounter card at a US university hospital and its 16 teaching affiliates during academic years 1997-1998 through 1999-2000. PARTICIPANTS: A total of 647 third-year medical students who completed patient encounter cards in 3 clerkships: family medicine, pediatrics, and internal medicine. MAIN OUTCOME MEASURES: Number of patient encounters, principal and secondary diagnoses, severity of diseases, and diagnostic procedures as recorded on patient encounter cards; concordance of patient encounter card data with medical records. RESULTS: Students completed 86 011 patient encounter cards: 48 367 cards by 582 students in family medicine, 22 604 cards by 469 students in pediatrics, and 15 040 cards by 531 students in internal medicine. Significant differences were found in students' case-mix of patients, the level of disease severity, and the number of diagnostic procedures performed across the 3 clerkships. Stability of the findings within each clerkship across 3 academic years and the 77% concordance of students' reports of principal diagnosis with faculty's confirmation of diagnosis support the reliability and validity of the findings. CONCLUSIONS: An instrument that facilitates students' documentation of clinical experiences can provide data on important differences among students' clerkship experiences. Data from this instrument can be used to assess the nature of students' clinical education.

Perceptions of medical school seniors of the current changes in the U.S. health care system.

Perceptions of medical school seniors about changes occurring in the health care environment were investigated. A survey was completed by 196 Jefferson Medical College seniors in the class of 1997. Of the respondents, 79% believed that cost reduction rather than quality of care is the primary consideration behind recent changes, 78% felt that managed care organizations hamper physicians' abilities to render optimal care, 83% maintained that the control of health care by insurance companies would lead to lower quality of care, 69% agreed that patients should have the freedom to seek a specialist's care without being referred by a primary care physician, 82% recommended that mentally ill patients should be referred to a mental health professional, and 82% believed that learning to work in a managed care environment should be an essential component of medical education. Assessment of student perceptions can assist in the development and implementation of appropriate curricular changes.

Outcome in sarcoidosis. The relationship of relapse to corticosteroid therapy.

STUDY OBJECTIVE: To determine the demographic, clinical, and radiographic characteristics of corticosteroid-treated patients with sarcoidosis who developed relapse following a period of clinical stability lasting longer than 1 month, and to compare these characteristics with those of a group of patients with sarcoidosis who were not treated. DESIGN: Historic, concurrent and prospective, nonrandomized, observational study. SETTING: Ambulatory sarcoidosis clinic in a university city hospital. PATIENTS: Over a 4-year calendar period, 337 patients with sarcoidosis were prospectively enrolled in a registry. One hundred eighteen patients were assigned to a spontaneous remission group when symptoms resolved without treatment, and 103 were assigned to an induced remission group when symptoms resolved following corticosteroid therapy and successful discontinuation. In 116 patients assigned to a recalcitrant group, therapy could not be stopped for 1 month or more owing to severity of symptoms or lack of compliance. We defined relapse as a recurrence of symptoms of sufficient severity to warrant treatment with corticosteroids, following a remission without treatment lasting greater than 1 month. INTERVENTION: Patients who were judged to be sufficiently symptomatic to preclude observation without treatment or who failed to respond to conservative treatment with topical or inhaled corticosteroids or nonsteroidal anti-inflammatory agents were treated with systemic corticosteroids at a target dose of 20 mg prednisone per day for 1 year. MEASUREMENTS AND RESULTS: We observed a 74% relapse rate in the induced remission group, but only an 8% relapse rate in the spontaneous remission group (p < 0.01). Relapse occurred with similar frequency in whites and African-Americans (20% vs 28%), despite a lower treatment rate in white patients than in African-Americans (43% vs 76%; p < 0.01). White patients maintained a sustained remission with twice the frequency of African-Americans (58% vs 29%; p < 0.01). During relapse, 40% of chest radiographs showed no change in type, but there was a significant increase in interstitial profusion (p < 0.05). Initial presentation with asymptomatic chest radiographic abnormalities, erythema nodosum, or peripheral adenopathy portended a favorable prognosis, with sustained remission in 60% of such patients lasting 130 +/- 226 months from time of diagnosis. In contrast, patients who presented with musculoskeletal complaints were nine times, and those with symptoms from hepatic involvement were three times more likely to suffer relapse than to sustain remission without receiving corticosteroids. Most relapses (50%) occurred between 2 and 6 months after discontinuing steroid therapy, but late relapse was not unusual, occurring more than 12 months after discontinuing steroid therapy in 20% of patients with induced remission. CONCLUSIONS: Relapse occurred frequently in patients with sarcoidosis who had been treated with corticosteroids, and rarely occurred in patients who had not been treated with corticosteroids in the past. The striking difference in relapse rate between treated and untreated patients suggests that patients with disease that would later be severe and protracted were almost unerringly identified early in their course. One explanation is that severe presenting symptoms portend a protracted and recurrent course; an alternative explanation is that corticosteroids contributed to the prolongation of the disease by delaying resolution.

Physicians' responsibilities and outcomes of medical care.

BACKGROUND: The federal government and many states have published hospital-specific data on resource use and outcomes of care. Both Pennsylvania and New York State have published data that identify physicians by name. These data are being released without a clear understanding of physicians' responsibilities and the impact of their behavior on patient outcomes. They also lack the clinical specificity necessary for appropriate comparisons of outcomes or processes of care. This article proposes a model for defining the responsibilities of physicians in providing medical care and describes a clinically specific approach to classifying patients for evaluation studies. A PROPOSED MODEL: Physicians' responsibilities require that they act as clinicians, managers, and teachers. Outcomes are affected by many factors--the practices of the individual physician, the contributions of the patient, the setting in which care is provided, and the social and physical environment. To enable clinically specific comparisons to be made, an approach to defining biological severity of illness based on the dimensions of location, etiology, and severity of the problem is described. CONCLUSION: Public release of data concerning quality of medical care implies a responsibility for the quality of the data being presented. Research needs to be performed to improve measurement tools, new personnel need to be adequately trained, and data that have clinical and statistical validity need to collected and analyzed.

Monoclonal antibody therapy for gram-negative sepsis: principles, applications, and controversies.

Gram-negative sepsis is a common event in hospitalized patients and is a leading cause of death in the United States. Endotoxin (lipopolysaccharide, LPS), a component of the cell wall of gram-negative microorganisms, is responsible for the cascade of events leading to the sepsis syndrome consisting of fever, tachycardia, tachypnea, and evidence of organ hypoperfusion. The lipid A region of endotoxin produces most of these biologic and toxic effects. Monoclonal IgM antibodies directed against the lipid A portion of endotoxin (anti-LPS MoAb) have been developed for the treatment of gram-negative sepsis. Results of two large-scale clinical trials suggest that these antibodies offer clinically and statistically significant reductions in mortality by a factor of about one-third. However, in both trials, this apparent beneficial effect was limited to particular subsets of patients, and no overall benefit was seen. These considerations, in addition to the likely high cost of the agents, pose questions about their ultimate use in the treatment of patients with gram-negative sepsis. Nevertheless, the logic of the approach, the demonstration of efficacy in disease models, and the advances in modern techniques of molecular biology all suggest that these or other closely related products will play a significant role in the treatment of this disorder.

A multicenter registry of patients with acute respiratory distress syndrome. Physiology and outcome.

In a multicenter registry conducted over 2 yr of patients with acute respiratory distress syndrome (ARDS), we enrolled 153 patients and collected data daily for 7 consecutive days and weekly thereafter until death or hospital discharge. The purposes of the registry were (1) to determine whether a more liberal definition of ARDS (PaO2/FIO2 < or = 250; bilateral pulmonary infiltrates within 7 days) than those commonly used would result in enrollment of patients earlier in their clinical course, and (2) to study the clinical course of the syndrome in survivors and nonsurvivors. The mortality rate was 54% and it was significantly greater in older versus younger patients (75% versus 37%) and in septic versus nonseptic patients (60% versus 43%). We found that the definition of ARDS used for the registry resulted in enrollment of patients 1 to 7 days earlier than was the case when other published definitions of ARDS were applied to the patient population. Fewer than 2% of the patients failed to meet one of the nonregistry definitions of ARDS within 7 days. The mortality rate was independent of the definition used to identify ARDS patients. Our results suggest that a more liberal definition of ARDS than those commonly used can result in identification of the same population of patients earlier in their clinical course.

Perspective: preventive isoniazid therapy and the liver.

The preventive use of isoniazid (INH) has been controversial since 1975, but official agencies continue to advocate the procedure. Cost-effectiveness and risk benefit studies of preventive INH use have come to conflicting conclusions. A review of eight such studies indicates an increasing tendency to minimize INH hepatotoxicity and to disregard the declining tuberculosis morbidity and mortality in countries in which INH prophylaxis has not been widely adopted. We report three cases of fatal INH-associated hepatitis that illustrate that this complication of preventive INH use remains a serious problem. Current recommendations that encourage wide use of preventive INH therapy are unwise because they inflict a risk of fatal hepatitis on compliant adults and older children who have little danger of tuberculosis while being difficult to deliver to the alcohol- and drug-addicted persons whose risk is high. Health departments and physicians should severely restrict preventive INH therapy.

P & T Committee response to evolving technologies: preparing for the launch of high-tech, high-cost products. Roundtable discussion.

P & T Committees are entering an exciting era in which the introduction of biotechnology-derived pharmaceuticals is providing life-saving opportunities for conditions for which there was little or no hope for a cure. The P & T Committee at Thomas Jefferson University Hospital has anticipated the challenge that these novel therapeutics present, and has already positioned itself for the pending approval of the first therapeutic human monoclonal antibody. Nebacumab (HA-1A, formerly known as Centoxin; by Centocor) will be used for the treatment of gram-negative sepsis. Although this antiendotoxin has a good side effect profile, its use also carries a high price tag. This will raise several difficult ethical issues once the product is introduced. In this exclusive Hospital Formulary roundtable, members of Thomas Jefferson's P & T Committee and Technology Assessment Subcommittee provide their insights for responsibly managing a high-tech, high-cost product such as nebacumab.

Recurrent noncardiac pulmonary edema accompanying pregnancy-induced hypertension.

Severe pulmonary edema occurred in a patient during the third trimester of two consecutive pregnancies, 17 months apart. Noncardiac origin of the pulmonary edema was demonstrated by normal pulmonary capillary wedge pressures, normal roentgenographic cardiac dimensions with absence of effusions, normal echocardiographic ejection fraction, and elevated thermodilution cardiac outputs; moderate reduction in serum albumin levels may have contributed. In the setting of pregnancy-induced hypertension, the development of ARDS on each occasion suggests a pathophysiologic link.

Physiology of aging related to outcome in the adult respiratory distress syndrome.

Thirty-nine patients with adult respiratory distress syndrome (ARDS) were enrolled in a study to identify potential age-related changes in organ system function that may help explain the apparent association between age and poor outcome in these patients. Criteria for enrollment included an arterial PO2-to-inspired O2 concentration ratio less than or equal to 200 in a clinical setting consistent with ARDS. Patients were excluded if they were less than 18 yr old, had clinical manifestations of congestive heart failure, were seropositive for the human immunodeficiency virus, or had stage II metastatic lung cancer. Patients were divided into two groups: those less than 60 yr old (mean 42 +/- 3 yr, n = 17) and those greater than or equal to 60 yr old (73 +/- 2 yr, n = 16). A group of six patients was analyzed as a separate subset based on a body temperature less than or equal to 97.5 degrees F at enrollment (hypothermic patients, 73 +/- 4 yr old). Sepsis was present in 67% of the nonhypothermic patients and in all the hypothermic patients. Mortality rates were 12% in the patients less than 60 yr and 69% in the nonhypothermic patients greater than or equal to 60 yr. All the hypothermic patients died. Sequential data obtained over 6 days were compared within and between groups. The following results were obtained. 1) The ratio of arterial PO2 to inspired O2 fraction was greater and the positive end-expiratory pressure used was significantly less in the patients greater than or equal to 60 yr old compared with the younger group.(ABSTRACT TRUNCATED AT 250 WORDS)

Infection with Mycobacterium avium complex in patients without predisposing conditions.

Pulmonary disease caused by Mycobacterium avium complex usually occurs in patients with chronic lung disease or deficient cellular immunity, and its prevalence is increasing. We describe 21 patients (mean age, 66 years) with such infection without the usual predisposing factors, representing 18 percent of the 119 patients surveyed. Seventeen women and 4 men were given a diagnosis of M. avium complex from 1978 to 1987, with a stable incidence over the decade, on the basis of pulmonary symptoms, abnormalities on chest films, positive cultures, and in 14, biopsy evidence of invasive disease. Most of the patients (86 percent) presented with persistent cough and purulent sputum, usually without fever or weight loss. The cough was present for a mean of 25 weeks before the correct diagnosis was made. Radiographic patterns of slowly progressive nodular opacities predominated (71 percent); only five patients had cavitary disease at presentation. All patients responded initially to antimycobacterial therapy, but eight eventually relapsed when it was stopped. Four patients died of progressive pulmonary infection caused by M. avium complex. The extent of the initial pulmonary involvement was greater in patients with progressive disease than in those whose condition improved. We conclude that pulmonary disease caused by the M. avium complex can affect persons without predisposing conditions, particularly elderly women, and that recognition of this disease is often delayed because of its indolent nature.

Prolonged exposure of neutrophils to saline or bronchoalveolar lavage fluid does not alter superoxide anion generation.

The role played by neutrophils (PMNs) in the genesis of lung injury in diverse clinical situations, such as bronchial asthma, idiopathic pulmonary fibrosis, and the adult respiratory distress syndrome, is an area of intensive investigation. Functional studies of PMNs, particularly those obtained from the alveoli by bronchoalveolar lavage, should shed light on their contribution to lung injury. However, it has not been demonstrated whether procedures used to harvest cells from the lung (bronchoalveolar lavage), particularly the potentially prolonged exposure to saline, commonly used to perform lavage, and other components of lavage fluid, can alter the functional characteristics of PMNs. In this report we demonstrate that a 2- to 3-hour exposure of neutrophils to saline from both humans and sheep in vitro does not alter the functional characteristics of PMNs as determined by superoxide anion generation after activation with phorbol myristate acetate (PMA; 6.96 +/- 0.44 vs. 7.60 +/- 0.32 nmol O2-/250,000 PMNs for control and saline-treated human cells, respectively, after a 45-min incubation with 10(-7) M PMA, and 4.73 +/- 0.30 vs. 4.50 +/- 0.42 nmol O2-/250,000 PMNs for control and saline-treated sheep cells). In a second series of experiments, we studied the effect of exposure of human PMNs to bronchoalveolar lavage fluid supernatants obtained from normal volunteers on superoxide anion generation by neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS)