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Biomedical subjects

B Levine

Publications and source records attributed to B Levine.

At least 19 recordsLinked to original sources

Long term intraparenchymal Ig secretion after acute viral encephalitis in mice.

Oligoclonal bands in the cerebrospinal fluid indicate intrathecal synthesis of Ig of restricted heterogeneity and are associated with a number of central nervous system inflammatory diseases. To gain better insight into the persistence of oligoclonal bands found in the central nervous system we studied mice infected with Sindbis virus (SV), a RNA virus that causes an acute, nonfatal encephalitis in mice. SV was inoculated intracerebrally into weanling mice and brains and spleens were harvested at various time points long after the acute encephalitis had resolved. A modified enzyme-linked immunoassay was used to study cultured B cells separated from the brain and spleen for their Ig isotype expression and specificity for SV. We used the polymerase chain reaction technique to detect SV RNA in brain. Three mo after inoculation 47% of the B cells found in brain are secreting antibody specific for SV structural proteins. By 1 yr 62% are SV specific. B cells secreting IgG2a predominate. Polymerase chain reaction data indicate that despite complete clearance of infectious virus by 7 days SV RNA is still present in brain at least 6 mo after infection. The data indicate that B cells in brain secrete antibody to SV long after the acute encephalitis has resolved. The persistence of SV RNA suggests that viral protein may continue to be made, providing the impetus for the continued presence of SV-specific B cells in the brain.

Animals

Measurement of azacyclonol in urine and serum of humans following terfenadine (Seldane) administration using gas chromatography-mass spectrometry.

A gas chromatographic-mass spectrometric (GC-MS) method is presented for the analysis of azacyclonol (AZA), a metabolite of terfenadine in serum and urine specimens. Following an alkaline extraction, AZA and an internal standard were derivatized using heptafluorobutyric anhydride. Fourier transform infrared spectrometry suggested that two sites on the AZA molecule were derivatized. GC-MS of the extracts had a limit of quantitation (LOQ) of 1 ng/ml and linear range of 1-1000 ng/ml in urine. Four volunteers were administered a therapeutic regimen of terfenadine followed by urine and serum specimen collection(s) during the next seven days. The results indicated that following a 60-mg dose of terfenadine each 12 h for five days, (1) AZA appears in urine within 2 h, (2) urine AZA concentrations were above the LOQ 72 h following the last dose, (3) peak urine concentrations were as high as 19,000 ng/ml, and (4) mean serum concentration following the ninth dose was 59 ng/ml.

Adult

PACS clinical experience at Georgetown University.

Georgetown University Hospital has been operating an image management and communications system (IMACS or PACS) for 3.5 years. This work was initially funded under the Army Medical Research and Development Command Digital Imaging Network Systems (DINS) project. The system was taken from a research system supporting only radiology tasks to one extended to clinical use, and has been used in clinical work for 3 years. This paper will summarize our PACS clinical experience and will describe the operational features implemented and those still necessary.

Computer Systems

Toxicological findings in military aircraft fatalities from 1986-1990.

Toxicological findings in all military aircraft fatalities investigated by the Division of Forensic Toxicology at the Armed Forces Institute of Pathology from 1986-1990 are presented. Carbon monoxide saturation levels greater than 10% were found in 4% of the 535 cases where appropriate specimens were collected. Positive ethanol findings were more indicative of postmortem formation than antemortem consumption. In only 1 case were abused drugs (cannabinoids in a passenger) detected. Other drugs identified included nicotine, chloroquine and over-the-counter analgesic agents, antihistamines and sympathomimetic drugs.

Accidents, Aviation

Persistence of viral RNA in mouse brains after recovery from acute alphavirus encephalitis.

Little is known about the relationship between recovery from acute viral encephalitis and the clearance of viral genetic material from the central nervous system. In a mouse model of Sindbis virus encephalitis, we have previously shown that clearance of infectious virus is mediated by antibody-induced restriction of viral gene expression rather than by cytotoxic destruction of virally infected cells. To explore whether Sindbis virus genomes persist in mouse brain after the clearance of infectious virus, we used reverse transcriptase-polymerase chain reaction amplification methods to detect Sindbis virus RNA in brain samples from immunocompetent BALB/c and antibody-treated immunodeficient scid/CB17 mice. RNA sequences from both the nonstructural region (NSP1 gene) and structural regions (E2 gene) of Sindbis virus were detected in the brains of all BALB/c and antibody-treated scid mice examined at 1, 2, and 3 months after infection. Additional BALB/c mouse brains were also positive at 8, 12, and 17 months after infection. To determine whether persistent RNA was capable of resuming unrestricted replication in the absence of the continuous presence of antiviral antibodies, viral titers were measured in the brains of scid mice at 1, 2, 3, and 6 months after antibody treatment. Viral reactivation was seen in scid mice treated with hyperimmune serum or a low dose of monoclonal antibody to the E2 envelope glycoprotein, but not in mice treated with a high dose of monoclonal antibody to E2. Replication of infectious virus isolated from scid mouse brain could be restricted by repeat treatment with immune serum, indicating that viral reactivation is not due to antibody-escape mutations. These results demonstrate that Sindbis virus can persist long term in a nonproductive form in mouse brain and suggest that the humoral immune response plays an important role in preventing viral reactivation.

Acute Disease

Clinical pathology testing recommendations for nonclinical toxicity and safety studies. AACC-DACC/ASVCP Joint Task Force.

Clinical pathology testing in nonclinical toxicity and safety studies is an important part of safety assessment. In recent years, clinical laboratory testing has rapidly expanded and improved. Some government regulatory agencies provide guidelines for clinical pathology testing in nonclinical toxicity and safety studies. To improve these testing guidelines and the resultant safety assessments, the American Association for Clinical Chemistry's Division of Animal Clinical Chemistry and the American Society for Veterinary Clinical Pathology formed a joint committee to provide expert recommendations for clinical pathology testing of laboratory species involved in subchronic and chronic nonclinical toxicity and safety studies. These recommendations include technical recommendations on blood collection techniques and hematology, serum chemistry, and urinalysis tests.

Animals

The immune response in viral encephalitis.

The central nervous system (CNS) offers a unique organ system in which to study viral immunopathogenesis. The presence of the blood-brain barrier that restricts entry of cells and protein, the restricted expression of MHC antigens and the nonrenewable nature of the neuronal cell population offer challenges to the immune system for viral clearance and increase the chances for viral persistence. We have used Sindbis virus encephalitis in mice as a model system for the study of the development of immune reactions in the CNS and clearance of virus from neurons. The immune response to this and other viral infections of the CNS probably are initiated in peripheral lymphoid tissue followed by entry of activated T cells into the cerebrospinal fluid, meninges, and brain parenchyma. During Sindbis virus infection class I and II MHC antigens are expressed extensively on microglia which may present viral antigen produced by the infected neurons. Full development of the inflammatory response requires virus-specific T cells, but participating cells include NK cells, gamma delta T cells, monocytes and B cells. The entry of Ig-secreting B cells corresponds with the appearance of increased amounts of IgG and IgA in the cerebrospinal fluid. Clearance of Sindbis virus from the brain was studied using persistently infected severe combined immunodeficient (scid) mice. Passive transfer of immune serum or immune T cells to these infected mice demonstrated that antibody to a surface glycoprotein of the virus eliminated virus by a noncomplemented-mediated, noncytolytic mechanism. Immune T cells had no effect on virus replication.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The justifications and controversies of panendoscopy--a review.

The triple endoscopies of direct laryngoscopy, bronchoscopy, and esophagoscopy, commonly known as panendoscopy, are frequent surgical procedures in otorhinolaryngology. Their purpose is to diagnose additional primary malignancies. The incidence of multiple synchronous primary malignancies has been reported between 3% and 13%. This unusually high rate is attributed to the process of field cancerization in which an anatomical region is exposed to a surface carcinogen and multifocal areas undergo irreversible change to multifocal malignancies. The majority of additional malignancies are diagnosed within 2 years of the index tumor's diagnosis, and are most consistently diagnosed within routine panendoscopy. Nevertheless, a significant percentage (40%) of additional primary malignancies present after this time and consequently, long-term follow-up is essential to the timely diagnosis of metachronous lesions. The predominant controversies surrounding panendoscopy involve the comparable diagnostic efficacies between endoscopic procedures and various radiologic studies. Although the operative complications reported for panendoscopy have been minimal, the expense is considerably greater than that of the respective radiologic alternatives. After a critical review of the literature, the use of endoscopy has been found to be superior to CXRs and barium swallows as the principal means of diagnosis of upper aerodigestive tract cancers. Specifically, bronchoscopy with bronchial washings should be obtained via passage of the bronchoscope through the endotracheal tube in order to decrease contamination. Positive washings are significant and demand further evaluation. Negative washings, on the other hand, yield little information.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchoscopy

Toxicologic findings in the USS Iowa disaster.

The toxicologic results from the 47 victims of the explosion on the USS Iowa are presented. Good correlation between carboxyhemoglobin saturations and cause of death was found. There were no correlations between blood cyanide concentrations and causes of death. Volatile analysis suggested postmortem ethanol production rather than antemortem ethanol ingestion. No drugs except nicotine were detected in any of the victims.

Carbon Monoxide

Comparison of Abbott fluorescence polarization immunoassay (FPIA) and Roche radioimmunoassay for the analyses of cannabinoids in urine specimens.

Abbott fluorescence polarization immunoassay (FPIA) and Roche Abuscreen radioimmunoassay (RIA) were compared qualitatively with 142 urine specimens containing 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid. Similar qualitative results were obtained in 132 specimens. When discrepent results were observed, all negative results were within 20% of the 100 ng/mL cut-off. We concluded that FPIA and RIA give comparable results to each other.

Cannabinoids

Protein depletion and metabolic stress in elderly patients who have a fracture of the hip.

A prospective study was performed to determine the effect of protein depletion and postoperative nutritional status on the outcome in sixty-three elderly patients who had been admitted to the hospital because of a fracture of the hip. The parameters that were used to determine the degree of protein depletion included levels of albumin, of prealbumin, and of transferrin; total lymphocyte count; and nitrogen-balance studies. The outcomes that were examined were the development of complications, the length of the stay in the hospital, the ability to return to the pre-fracture level of function, and over-all survivorship. The hypothesis was that the acute fracture and the subsequent operation are severe stresses in these elderly, often compromised patients. The results supported the hypothesis. Thirty-seven patients (58 per cent) in the study group were in a protein-depleted state during the period of hospitalization. The patients who were protein-depleted had a higher prevalence of complications, were less likely to return to their pre-fracture environment, and tended to stay in the hospital longer, as compared with the nonprotein-depleted patients. Survivorship analysis showed that protein-depleted patients had a significantly lower probability of survival one year after the fracture of the hip (p = 0.02). Elderly patients who sustain the trauma of a fracture of the hip should be managed appropriately with regard to intake of nutrients in the postoperative period.

Aged

Antibody-mediated clearance of alphavirus infection from neurons.

Humoral immunity is important for protection against viral infection and neutralization of extracellular virus, but clearance of virus from infected tissues is thought to be mediated solely by cellular immunity. However, in a SCID mouse model of persistent alphavirus encephalomyelitis, adoptive transfer of hyperimmune serum resulted in clearance of infectious virus and viral RNA from the nervous system, whereas adoptive transfer of sensitized T lymphocytes had no effect on viral replication. Three monoclonal antibodies to two different epitopes on the E2 envelope glycoprotein mediated viral clearance. Treatment of alphavirus-infected primary cultured rat neurons with these monoclonal antibodies to E2 resulted in decreased viral protein synthesis, followed by gradual termination of mature infectious virion production. Thus, antibody can mediate clearance of alphavirus infection from neurons by restricting viral gene expression.

Alphavirus

Mycobacterium kansasii: a cause of treatable pulmonary disease associated with advanced human immunodeficiency virus (HIV) infection.

OBJECTIVE: To assess the clinical features and response to therapy of Mycobacterium kansasii infection in patients with human immunodeficiency virus (HIV) infection. DESIGN: We reviewed the records of all patients with M. kansasii and HIV infection treated between January 1985 and June 1990. SETTING: The Johns Hopkins Hospital, Baltimore, Maryland. RESULTS: Nineteen patients with M. kansasii and HIV infection were identified; 14 patients had exclusive pulmonary infection, 3 patients had pulmonary and extrapulmonary infection, and 2 patients had exclusive extrapulmonary infection. At the time of diagnosis of M. kansasii infection, the median CD4+ lymphocyte count was 49 cells/microL (range, 0 to 198 cells/microL), and 16 of 19 patients had a previous diagnosis of the acquired immunodeficiency syndrome (AIDS). All 17 patients with pulmonary infection presented with fever and cough of at least 2 weeks duration. Chest radiographs showed either focal upper lobe infiltrates (n = 8) or diffuse interstitial infiltrates (n = 9); 9 patients also had thin-walled cavitary lesions. Nine patients with pulmonary M. kansasii infection were treated with antituberculosis chemotherapy, with resolution of fever and respiratory symptoms, improvement of radiographic infiltrates, and sputum conversion; 1 patient with M. kansasii osteomyelitis also responded to antituberculosis therapy. Autopsies done on 3 treated patients did not reveal any evidence of M. kansasii infection. Nine patients did not receive any antituberculosis chemotherapy; 2 untreated patients developed progressive cavitary pulmonary disease and died from M. kansasii pneumonia. CONCLUSIONS: Mycobacterium kansasii causes serious and potentially life-threatening pulmonary disease in patients with advanced HIV-related immunosuppression. In contrast to previous reports, our findings indicate that disease produced by M. kansasii in patients with HIV infection is responsive to antituberculosis chemotherapy.

Adult

Nutrition research in the clinical setting.

The role of calcium in the prevention and treatment of disease is timely and a number of our collaborative studies are being conducted under the auspices of our Clinical Nutrition Research Unit (CNRU) investigators. The CNRU is a grant that was awarded by the National Institutes of Health to Memorial Sloan-Kettering Cancer Center, New York Hospital-Cornell University Medical Center and The Rockefeller University in 1980. The grant was expanded in 1985 to include the Hospital for Special Surgery and North Shore University Hospital. The purpose of this program, now in its 10th y, is to advance research, improve nutrition education, and translate the knowledge gained from research into improved prevention and treatment programs for patient care. Our collaborative CNRU now involves these five academic institutions, each with its own special resources and areas of expertise. We bring together clinical and basic scientists from a variety of subspecialties who share a common interest in specific aspects of nutrition.

Calcium, Dietary

Low rate of treatment of hypercholesterolemia by cardiologists in patients with suspected and proven coronary artery disease.

BACKGROUND: Although specific guidelines for the treatment of hypercholesterolemia have been published, it is not known whether physicians treating patients likely to have lipid disorders have adopted the recommendations. METHODS AND RESULTS: The approach of cardiologists to the treatment of hypercholesterolemia in a metropolitan teaching hospital was assessed by interviewing patients with chest pain who were admitted for coronary angiography in 1988-1989 and by measuring fasting blood lipid profiles. At 1 month and again 12-24 months later, patients were contacted by telephone to determine if there had been any changes in treatment. Of 95 patients evaluated, 81 had coronary artery disease. Only 17% of those with high levels of total cholesterol and/or low density lipoprotein cholesterol were being actively treated with diet and/or drugs. In the remaining patients, either lipid studies had not been done or abnormal results had not been addressed. There was little change in treatment approach during the month after the diagnostic procedure. Furthermore, the experience was similar in those patients subjected to coronary revascularization. One to 2 years after the initial intervention, 69 of the original study group could be contacted again. Although active dietary or pharmacological therapy was initiated in some individuals during this interval, it was stopped in others. Thirty-five percent of hypercholesterolemic patients were receiving targeted therapy. CONCLUSIONS: Thus, only a small proportion of patients with documented coronary artery disease and hypercholesterolemia were being actively treated for their lipid disorder, suggesting that the published treatment guidelines have not yet been fully accepted. However, an encouraging improvement in frequency of treatment of hypercholesterolemia was documented during the 1-2-year observation period.

Cardiology

Toxicological findings in Federal Aviation Administration general aviation accidents.

Blood, urine, and tissue specimens were received from 377 Federal Aviation Administration (FAA) aviation fatalities during fiscal year 1989. Carbon monoxide at less than 10% saturation was found in 94% of the cases, and cyanide at less than 0.5 mg/L was found in 96% of the cases. Ethanol at greater than 10 mg/dL was found in 14.8% of the cases, but only 4.5% were determined to be due to ethanol ingestion from toxicological findings. Excluding nicotine and ethanol, 12.6% of the cases were positive for one or more drugs. Acetaminophen and salicylate were the most frequently found drugs. Cannabinoids were found in 1.3% of the cases and benzoylecgonine in 1.6%. There was minimal use of therapeutic drugs that cause central nervous system depression or stimulation. These results show no consistent pattern of drug involvement in civilian aviation fatalities.

Accidents, Aviation