John N. Dowling

The Transplanted Kidney as a Source of Cytomegalovirus Infection

To determine the incidence of cytomegalovirus infection in renal-transplant recipients we followed 32 prospectively for six months after operation. As judged by serologic change and virus isolation the infection rate for the entire group was 66 per cent (21 of 32 patients) - 59 per cent (13 of 22) for seronegative patients and 80 per cent (eight of 10) for seropositive patients. Of 10 seronegative patients who received kidneys from seronegative donors, only three became infected. However, of 12 seronegative patients who received kidneys from seropositive donors, 10 became infected. Thus, there was a significant correlation between development of infection and seropositivity of the donor (P = 0.03), particularly when the recipient was seronegative (P = 0.02). Five possible and four definite recognizable clinical illnesses were associated with cytomegalovirus infection; all except two were in initially seronegative subjects who received kidneys from seropositive donors. Primary infection and disease in nonimmune recipients may be caused by cytomegalovirus transmitted by the kidneys of latently infected seropositive donors.

ConText: An algorithm for determining negation, experiencer, and temporal status from clinical reports

In this paper we describe an algorithm called ConText for determining whether clinical conditions mentioned in clinical reports are negated, hypothetical, historical, or experienced by someone other than the patient. The algorithm infers the status of a condition with regard to these properties from simple lexical clues occurring in the context of the condition. The discussion and evaluation of the algorithm presented in this paper address the questions of whether a simple surface-based approach which has been shown to work well for negation can be successfully transferred to other contextual properties of clinical conditions, and to what extent this approach is portable among different clinical report types. In our study we find that ConText obtains reasonable to good performance for negated, historical, and hypothetical conditions across all report types that contain such conditions. Conditions experienced by someone other than the patient are very rarely found in our report set. A comprehensive solution to the problem of determining whether a clinical condition is historical or recent requires knowledge above and beyond the surface clues picked up by ConText.

Classifying free-text triage chief complaints into syndromic categories with natural languages processing

OBJECTIVE Develop and evaluate a natural language processing application for classifying chief complaints into syndromic categories for syndromic surveillance. INTRODUCTION Much of the input data for artificial intelligence applications in the medical field are free-text patient medical records, including dictated medical reports and triage chief complaints. To be useful for automated systems, the free-text must be translated into encoded form. METHODS We implemented a biosurveillance detection system from Pennsylvania to monitor the 2002 Winter Olympic Games. Because input data was in free-text format, we used a natural language processing text classifier to automatically classify free-text triage chief complaints into syndromic categories used by the biosurveillance system. The classifier was trained on 4700 chief complaints from Pennsylvania. We evaluated the ability of the classifier to classify free-text chief complaints into syndromic categories with a test set of 800 chief complaints from Utah. RESULTS The classifier produced the following areas under the ROC curve: Constitutional = 0.95; Gastrointestinal = 0.97; Hemorrhagic = 0.99; Neurological = 0.96; Rash = 1.0; Respiratory = 0.99; Other = 0.96. Using information stored in the systems semantic model, we extracted from the Respiratory classifications lower respiratory complaints and lower respiratory complaints with fever with a precision of 0.97 and 0.96, respectively. CONCLUSION Results suggest that a trainable natural language processing text classifier can accurately extract data from free-text chief complaints for biosurveillance.

ConText: An Algorithm for Identifying Contextual Features from Clinical Text

Applications using automatically indexed clinical conditions must account for contextual features such as whether a condition is negated, historical or hypothetical, or experienced by someone other than the patient. We developed and evaluated an algorithm called ConText, an extension of the NegEx negation algorithm, which relies on trigger terms, pseudo-trigger terms, and termination terms for identifying the values of three contextual features. In spite of its simplicity, ConText performed well at identifying negation and hypothetical status. ConText performed moderately at identifying whether a condition was experienced by someone other than the patient and whether the condition occurred historically.

Opportunistic Lung Infection Due to Pittsburgh Pneumonia Agent

Eight immunosuppressed patients had pneumonia due to Pittsburgh Pneumonia Agent (PPA), a gram-negative, weakly acid-fast bacterium cultivatable only in embryonated eggs and guinea pigs and distinct from Legionella pneumophila. The diagnosis was established by isolation of the agent from lung or visualization of the organism in lung tissue. The clinical presentations, radiographic abnormalities and pathology were not specific. The most consistent feature associated with the disease was the recent institution of daily high-dose corticosteriod therapy in all patients. Five of the eight patients died despite broad-spectrum antibiotic and antituberculous therapy. Anti-microbial activity against PPA was demonstrated for sulfamethoxazole combined with trimethoprim, for rifampin and for erythromycin with an egg-protection assay. Serologic studies with an indirect fluorescent-antibody technic suggested that seroconversion or high titers may be a sensitive test for PPA disease. PPA appears to be a newly recognized cause of life-threatening bacterial pneumonia in immunosupressed patients.

Fever detection from free-text clinical records for biosurveillance

Abstract Automatic detection of cases of febrile illness may have potential for early detection of outbreaks of infectious disease either by identification of anomalous numbers of febrile illness or in concert with other information in diagnosing specific syndromes, such as febrile respiratory syndrome. At most institutions, febrile information is contained only in free-text clinical records. We compared the sensitivity and specificity of three fever detection algorithms for detecting fever from free-text. Keyword CC and CoCo classified patients based on triage chief complaints; Keyword HP classified patients based on dictated emergency department reports. Keyword HP was the most sensitive (sensitivity 0.98, specificity 0.89), and Keyword CC was the most specific (sensitivity 0.61, specificity 1.0). Because chief complaints are available sooner than emergency department reports, we suggest a combined application that classifies patients based on their chief complaint followed by classification based on their emergency department report, once the report becomes available.

Properties of an acid phosphatase from Legionella micdadei which blocks superoxide anion production by human neutrophils

The high-speed supernatant (100,000 g, 1 h) obtained after centrifuging a suspension of Legionella micdadei that had been freeze-thawed and sonicated contained (i) considerable acid phosphatase activity when assayed using 4-methylumbelliferyl phosphate (MUP) as the substrate, and a factor that blocked superoxide anion production by human neutrophils stimulated with f-Met-Leu-Phe. Chromatography of the extract on a hydroxylapatite column resolved two acids phosphatases (designated ACP1 and ACP2). Subsequent chromatography of ACP2 on a Sephadex G-150 column revealed coincident elution of phosphatase activity and neutrophil blocking activity. When heated at 45 degrees C for various periods of time, the phosphatase activity of the acid phosphatase preparation was lost at the same rate as the ability of the preparation to block superoxide anion production by neutrophils. Furthermore, preincubation of neutrophils and acid phosphatase together in the presence of a heteropolymolybdate complex that inhibits the phosphatase eliminated the effect of the L. micdadei phosphatase on neutrophil superoxide anion production. ACP2 had the following properties: pH optimum, 6.0; Km for MUP, 3.8 mM; isoelectric point, 4.5; substrate specificity, MUP greater than ADP greater than phosphoenolpyruvate greater than phosphothreonine greater than phosphoserine greater than phosphotyrosine; molecular weight (estimated by sucrose density gradient centrifugation and gel filtration chromatography), 71,000-86,000. These results indicate that a cell-associated phosphatase may play a role in the virulence of L. micdadei.

Diagnosis of pneumonitis in immunocompromised patients by open lung biopsy

The records of 59 immunocompromised patients with fever and pulmonary infiltrates who underwent open lung biopsy, were reviewed. A specific diagnosis was made by lung biopsy in 49 (83%) patients, and in 32 instances (54%) the diagnosis was a treatable infection. Only two (3.4%) false‐negative biopsies occurred. Transplant recipients were more likely to have a specific, treatable pneumonia (74%) than patients with a reticuloendothelial malignancy (42%, P < 0.05). This was due to a greater frequency of bacterial pneumonias, primarily due to Legionella, in transplant recipients (P < 0.01). However, obtaining a specific diagnosis by lung biopsy did not appear to improve outcome. Seventeen of 32 (53%) patients with treatable infections survived, compared to 8 of 16 (50%) with specific, but untreatable, diagnosis and 6 of 11 (55%) with nondiagnostic biopsies. Advanced age and a low platelet count were predictive of death in both transplant recipients and patients with leukemia and lymphoma (P < 0.05); a high serum creatinine was an additional predictor in renal transplant recipients.

Hydrolysis of phosphoproteins and inositol phosphates by cell surface phosphatase of Leishmania donovani

Leishmania donovani promastigotes contain intense tartrate-resistant cell surface acid phosphatase (ACP1) which blocks superoxide anion production by activated human neutrophils [A.T. Remaley et al. (1984) J. Biol. Chem, 259, 11173-11175]. An extensively purified preparation of ACP1 dephosphorylates several phosphoproteins which are phosphorylated at serine residues; these include: pyruvate kinase (Km 1.6 microM; Vmax 71.4 U (mg protein)-1), phosphorylase kinase (Km 0.076 microM; Vmax 5.4 U (mg protein)-1) and histones (Km 4.86 microM; Vmax 2.2 U (mg protein)-1). However, the specific activity of the leishmanial phosphatase on these phosphoproteins is very low as compared to other phosphoprotein phosphatases. The phosphatase activity of ACP1 was also low on phosphohistone phosphorylated at tyrosine residues. Phosphatidylinositol-4,5-diphosphate (PIP2) and inositoltriphosphate (IP3) were also tested as ACP1 substrates. PIP2 was hydrolyzed rapidly by ACP1. The rate of hydrolysis of PIP2 was higher at pH 6.8 (Km 2.35 microM; Vmax 107 X 10(3) U (mg protein)-1) than at pH 5.5 (Km 4.16 microM; Vmax 71 X 10(3) U (mg protein)-1). 32P-labeled IP3 was also a substrate for ACP1; the hydrolysis products consisted of a mixture of inositoldiphosphate and inositolmonophosphate. ACP1 and ten other phosphatases were tested for their ability to dephosphorylate proteins and to inhibit O2- production by stimulated human neutrophils. There was no correlation between the protein phosphatase activity of the acid- and alkaline phosphatases and their ability to block neutrophil O2- production. The results indicate that ACP1 probably blocks the production of reduced oxygen intermediates by a mechanism that does not involve dephosphorylation of phosphoproteins; however, the possibility that the parasites phosphatase affects phagocyte metabolism by degrading PIP2 or IP3 should be considered.

Evaluation of training with an annotation schema for manual annotation of clinical conditions from emergency department reports.

OBJECTIVE Determine whether agreement among annotators improves after being trained to use an annotation schema that specifies: what types of clinical conditions to annotate, the linguistic form of the annotations, and which modifiers to include. METHODS Three physicians and 3 lay people individually annotated all clinical conditions in 23 emergency department reports. For annotations made using a Baseline Schema and annotations made after training on a detailed annotation schema, we compared: (1) variability of annotation length and number and (2) annotator agreement, using the F-measure. RESULTS Physicians showed higher agreement and lower variability after training on the detailed annotation schema than when applying the Baseline Schema. Lay people agreed with physicians almost as well as other physicians did but showed a slower learning curve. CONCLUSION Training annotators on the annotation schema we developed increased agreement among annotators and should be useful in generating reference standard sets for natural language processing studies. The methodology we used to evaluate the schema could be applied to other types of annotation or classification tasks in biomedical informatics.