trans activation of granulocyte-macrophage colony-stimulating factor and the interleukin-2 receptor in transgenic mice carrying the human T-lymphotropic virus type 1 tax gene.

Three lines of transgenic mice carrying the human T-cell lymphotropic virus type 1 tax gene have previously been reported to develop neurofibromas composed of perineural fibroblasts (S. H. Hinrichs, M. Nerenberg, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1340-1343, 1987; M. Nerenberg, S. H. Hinrichs, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1324-1329, 1987). Tumors from these mice and tumor cell lines derived from them expressed high levels of tax RNA and protein. They also expressed high levels of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene as measured by proliferative responses of FD-CP1 target cells using conditioned media from tumor cells and by Northern (RNA) blot analysis of RNA from tumors and tumor cell lines. Although other tissues, such as salivary glands and muscles, in the transgenic mice also expressed high levels of tax, they did not express the gene for GM-CSF. This indicates that tissue-specific cellular factors, in addition to tax, are required for GM-CSF gene expression. Systemic effects of excessive GM-CSF production were demonstrated by infiltration of polymorphonuclear leukocytes into tumor tissues which are not necrotic, by peripheral granulocytosis, and by splenomegaly resulting from myeloid hyperplasia. The interleukin-2 (IL-2) receptor was also found to be expressed by the tumors and tumor cell lines as measured by IL-2-binding and cross-linking studies. This is the first demonstration that the IL-2 receptor can be activated by tax in a nonlymphoid cell type. These in vivo findings are consistent with other reports which have demonstrated in vitro cis-regulatory elements within the 5'-flanking regions of the genes for GM-CSF and the IL-2 receptor which are responsive to trans activation by the tax gene.

Soluble interleukin-2 receptor levels in patients with undifferentiated and lymphoblastic lymphomas: correlation with survival.

We have been able to detect soluble interleukin-2 receptors (IL-2R) in pretreatment sera from 80 patients with undifferentiated lymphoma (predominantly Burkitt's lymphoma) and lymphoblastic lymphoma. The demonstration of IL-2R in lymphoma-derived cell lines by immunoprecipitation and direct staining indicates that IL-2R is synthesized by the tumor cells. Comparisons were made with two other subject groups: 42 sarcoma patients and 17 normal individuals. The distribution of soluble IL-2R values for lymphoma patients (geometric mean, 1,132 U/mL) was significantly greater than that of sarcoma patients (geometric mean, 332 U/mL; P = .0001) or normal individuals (geometric mean, 238 U/mL; P = .0001). Patients with undifferentiated lymphoma stages B, C, and D had significantly higher soluble IL-2R values (geometric mean, 1,648 U/mL) than stages A and AR (geometric mean, 706 U/mL; P = .0001) or lymphoblastic lymphoma (geometric mean, 826 U/mL; P = .0002). Within the lymphoma group, the soluble IL-2R level was found to be the most significant prognostic indicator of disease-free interval and survival when compared with other previously recognized factors such as histology, stage, bone marrow involvement at presentation, lactic dehydrogenase (LDH), uric acid (UA), and age. No factor was significantly associated with response to therapy, ie, the initial achievement of complete remission (CR) status, although small numbers of patients with a partial response limit interpretation. Soluble IL-2R levels were measured serially in two patients and were found to be elevated at presentation or relapse and to decrease to normal levels during periods of disease remission. IL-2R appears to reflect tumor burden and may prove to be a useful and specific marker for lymphoid tumors.

Long-term intravenous antibiotic therapy in chronic osteomyelitis.

Because the optimal treatment of chronic osteomyelitis is not well established, we studied the efficacy of prolonged (three months or more) outpatient intravenous antibiotic therapy via a Hickman catheter. Seventeen patients were entered into our protocol (13 with chronic osteomyelitis, three with chronic septic arthritis, and one with subacute osteomyelitis). Pseudomonas aeruginosa was the most common bone isolate, followed by Staphylococcus aureus. Most patients had polymicrobial isolates. Patients were followed up with clinical examinations, serial measurements of erythrocyte sedimentation rate, and scans using technetium Tc 99m medronate and gallium citrate Ga 67. Of the ten patients with chronic osteomyelitis who completed therapy, eight were considered cured. After further follow-up, three of the cured patients had recurrences requiring additional therapy.

Epidural abscess, vertebral destruction, and paraplegia caused by extending infection from an aspergilloma.

An aspergilloma developed in a lung cyst in a 53-year-old man. Aspergillus infection then contiguously spread to the epidural space, causing an abscess, vertebral destruction, and paraplegia at the level of T4. Chronic alcoholism, liver cirrhosis, and corticosteroid treatment may have been predisposing factors in this patient. Although Aspergillus epidural abscess has been described infrequently, this complication has not been described in association with an aspergilloma. Symptoms, signs, or roentgenographic or laboratory findings suggestive of vertebral or meningeal pathologic lesions in patients with aspergilloma should alert the physician to the possibility of contiguous spread of infection.

Dysgonic fermenter 3-associated gastrointestinal disease in a patient with common variable hypogammaglobulinemia.

A gram-negative bacteria designated DF-3 was cultured on multiple occasions from stool samples of a patient with common variable hypogammaglobulinemia and chronic diarrhea. Antibiotic therapy resulted in elimination of the organism and resolution of the patient's symptoms. DF-3 has not been linked previously to human disease; because of its fastidious growth characteristics and unique isolation requirements, it may be a rarely identified cause of diarrhea and other gastrointestinal symptoms in immunocompromised patients.

Successful treatment of post-mitral valve annuloplasty Aspergillus flavus endocarditis.

Aspergillus endocarditis is associated with a very high mortality. Of approximately 67 cases reported in the English language literature, there have been only two known survivors. This report describes a patient with Aspergillus flavus endocarditis after mitral valve annuloplasty who recovered with combined surgical and antifungal therapy. This is the first successfully treated case due to A. flavus and the first involving an annuloplasty ring.

Spinal cord aspergillus invasion--complication of an aspergilloma.

Acute paraplegia developed in a 53-year-old man with pulmonary aspergilloma because of contiguous extension of Aspergillus infection to the epidural and subdural spaces and spinal cord. Histopathologic findings of the spinal cord showed Aspergillus hyphae penetrating the myelin sheath and myelomalacia, predominantly in the anterior and lateral columns. To the authors' knowledge, there have been no previous descriptions or illustrations of spinal cord involvement and the pathologic changes caused by Aspergillus infection.

An objective analysis of process errors in trauma resuscitations.

OBJECTIVE: A computer-based system to apply trauma resuscitation protocols to patients with penetrating thoracoabdominal trauma was previously validated for 97 consecutive patients at a Level 1 trauma center by a panel of the trauma attendings and further refined by a panel of national trauma experts. The purpose of this article is to describe how this system is now used to objectively critique the actual care given to those patients for process errors in reasoning, independent of outcome. METHODS: A chronological narrative of the care of each patient was presented to the computer program. The actual care was compared with the validated computer protocols at each decision point and differences were classified by a predetermined scoring system from 0 to 100, based on the potential impact on outcome, as critical/noncritical/no errors of commission, omission, or procedure selection. RESULTS: Errors in reasoning occurred in 100% of the 97 cases studied, averaging 11.9/case. Errors of omission were more prevalent than errors of commission (2. 4 errors/case vs 1.2) and were of greater severity (19.4/error vs 5. 1). The largest number of errors involved the failure to record, and perhaps observe, beside information relevant to the reasoning process, an average of 7.4 missing items/patient. Only 2 of the 10 adverse outcomes were judged to be potentially related to errors of reasoning. CONCLUSIONS: Process errors in reasoning were ubiquitous, occurring in every case, although they were infrequently judged to be potentially related to an adverse outcome. Errors of omission were assessed to be more severe. The most common error was failure to consider, or document, available relevant information in the selection of appropriate care.

Effect of bone biopsy in guiding antimicrobial therapy for osteomyelitis complicating open wounds.

BACKGROUND: Osteomyelitis associated with infected overlying wounds represents a difficult diagnostic and therapeutic problem; bone biopsies can be done during debridement of the overlying wounds, but it is unclear how often the results of these bone cultures actually affect subsequent antibiotic decisions. The present study was undertaken to evaluate the usefulness of bone biopsies in guiding antibiotic therapy for this type of osteomyelitis. METHODS: Culture results of 44 bone biopsies taken during surgical debridement in 41 patients over the period from June 1994 to August 1998 were compared with those from the overlying wounds to determine whether the data affected the subsequent choice of antibiotics. The study design was that of a retrospective chart review in which the standard operative and microbiological procedures in place at the Milwaukee Veterans Affairs Medical Center were used. RESULTS: Sixty-one wound and 55 bone isolates were obtained during this study. Thirty-one isolates were found in bone, but not the overlying wound; diphtheroids were the most common organism obtained in this fashion. Correlation between wound and bone isolates was generally poor. Antibiotics were subsequently changed in 20 of the 44 cases after results of the bone biopsy became known, with the bone isolates already being covered in 10 cases and the bone biopsy results ignored in 14 cases. CONCLUSION: Because bone biopsy results seem to aid in tailoring antibiotic therapy in almost half the cases when bone is sampled during wound debridement surgery, this technique may be very helpful in certain cases and should be regularly undertaken when these procedures are carried out.

On-line quality [corrected] assurance in the initial definitive management of multiple trauma: evaluating system potential.

The TraumAID system has been designed to provide on-line decision support throughout the initial definitive management of injured patients. Here we describe its retrospective evaluation and the use we subsequently made of judges comments on the validation data to evaluate TraumaTIQ, a new critiquing interface for TraumAID, investigating the question of whether, with timely recording of information, a system could produce commentary in line with that of human experts. Our results show that (1) comparable commentary can be produced, and (2) validation studies, which take great time and effort to conduct, can produce useful data beyond their original design goals.

Foley catheter extraction of blunt esophageal foreign bodies.

The case is reported of a successful Foley catheter extraction of two superimposed coins from the esophagus of an 8-year-old girl. The presence of the second coin was suspected only on review of the lateral cervical radiograph. In a previous report, failure to initially diagnose the presence of an additional coin resulted in an endoscopic failure to clear the esophagus. The technical aspects of Foley extraction are reviewed along with the controversy surrounding the procedure. Series totaling 294 cases document a cumulative success rate of 85% without significant complications. The technique, when performed by airway experts, is concluded to be a viable alternative to endoscopic removal. Lateral films, fluoroscopic extraction, and barium studies in select cases are recommended as safeguards against missing nonobvious foreign bodies of the esophagus.

Needle aspiration of breast masses in the emergency department.

The discovery of a breast mass is often the source of great concern for a patient. The mass may, however, be no more than a benign cyst that may be treated in the emergency department. This article describes the technique of needle aspiration--a simple, safe procedure that in many cases is both therapeutic and curative.

Topical cocaine prior to treatment of penile tourniquet syndrome.

A case of the penile tourniquet syndrome is reported in a 5-year-old boy. Release of the constricting strands of hair was possible only after topical cocaine achieved adequate local anesthesia. The syndrome is briefly reviewed and emergency care recommendations are made.