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Biomedical subjects

R Costello

Publications and source records attributed to R Costello.

At least 91 records · Page 5Linked to original sources

An NMR blood test for cancer: a critical assessment.

An evaluation of the reproducibility and accuracy of the NMR human blood test for cancer described by Fossel, E. T., Carr, J. M. and McDonagh, J., (New England Journal of Medicine 315, 1369-1376) in 1986 has been conducted jointly at the National Cancer Institute-Frederick Cancer Research Facility, Frederick, MD (NCI-FCRF) and the National Research Council, Ottawa, Canada (NRC). The influences on the test of the following were studied: (a) subject fasting; (b) sample collection, storage and handling; (c) use of plasma or serum; (d) variations of test results from the same individual with time; (e) NMR observation parameters including field strength and temperature; and (f) variations in obtaining the Fossel Index (FI) (a number defined by Fossel and co-workers as the average of the widths at half height of the regions in the NMR spectrum of human plasma at 1.3 and 0.88 ppm) by different people from the same plotted spectrum. This test was found to be reproducible but not accurate for screening a general asymptomatic population. The accuracy is defined in terms of the sensitivity, specificity, and predictive values of the test. The accuracy of the test results from our laboratories is compared with the accuracies from other laboratories including Fossel's. The correlation of the Fossel Index with total triglyceride content in the serum has been confirmed by analysing blood components using the following technologies: KBr density gradient centrifugation, high resolution agarose gel electrophoresis, high performance gel permeation chromatography, and chemical analysis.

Blood Chemical Analysis↗

Monoclonal and oligoclonal immunoglobulins in the serum of patients with B-chronic lymphocytic leukemia.

The incidence of monoclonal and oligoclonal immunoglobulins (paraproteins) was determined in serum samples of 45 chronic lymphocytic leukemia (B-CLL) patients using the high-resolution agarose gel electrophoresis technique combined with immunofixation. Paraproteins were identified in 25 of the 45 patients tested. Twelve paraproteins were monoclonal and 13 oligoclonal. IgG kappa and/or lambda immunoglobulin isotypes were found in 17/25 of these patients. No correlation of the lymphocyte cell morphology and the presence of paraproteins was demonstrated. The high frequency of serum oligoclonal immunoglobulins in B-CLL indicates that more than one lymphocyte clone may be present in this disease.

B-Lymphocytes↗

Identification of HIV-specific oligoclonal immunoglobulins in serum of carriers of HIV antibody.

Zone electrophoresis on agarose gel was performed on serum samples from HIV-antibody carriers and negative controls. Nitrocellulose strips precoated with an HIV preparation were then placed on top of the gels and developed by an immunoblotting procedure. A positive reaction was demonstrated between the HIV antigens and the HIV-antibody-positive serum samples with hypergammaglobulinemia and oligoclonal IgG bands. A negative reaction was found between the HIV antigens and HIV-antibody-negative serum samples from a normal person and a patient with monoclonal gammopathy. The presence of oligoclonal IgG bands in the serum of HIV-antibody carriers, and their positive identification with HIV antigens, indicates a specific immune response of the host to the HIV infection and supports the use of oligoclonal IgG bands as markers to follow the course of HIV infection.

Antibodies, Viral↗

Oligoclonal immunoglobulins in the sera of healthy subjects at risk for AIDS.

Analysis of serum samples from 68 healthy subjects seropositive for HTLV-III antibodies was performed by high-resolution zone electrophoresis. A high incidence of oligoclonal immunoglobulin bands was detected in the sera of these subjects compared with absence of these bands in the sera of healthy seronegative controls. Identification of the immunoglobulin bands by immunofixation revealed a single heavy chain IgG, single kappa and mixed kappa and lambda light chains. The presence or absence of oligoclonal immunoglobulin bands, determined by zone electrophoresis in serum samples from healthy subjects who have been exposed to HTLV-III, may prove to be a useful biochemical marker for following the course of infection and for determining a prognosis.

Acquired Immunodeficiency Syndrome↗

A comparison between chemical analysis and magnetic resonance imaging with the clinical diagnosis of multiple sclerosis.

Ninety-five patients suspected of having multiple sclerosis (MS) were evaluated by medical history and neurologic examination. Based on this evidence they were divided into three groups: clinically definite MS, not-definite MS, and not MS. The adjunct tests, chemical analysis, and magnetic resonance imaging (MRI), were also performed to assess the diagnosis of MS. Chemical analyses of paired serum and cerebrospinal fluid (CSF) samples were performed to identify oligoclonal immunoglobulin bands and to estimate both the albumin quotient and the IgG index. A positive correlation was found between the chemical test results and definite MS in 73 of 73 cases. In 11 of 12 cases of not-definite MS the chemical results were positive for MS. A positive correlation was also found between ten of ten cases that were not MS and negative chemical test results. MRI scans were positive for MS in 48 of 51 clinically definite MS cases and in 4 of 4 not-definite MS cases. MRI scans were negative for MS in five of six cases that were not MS. These findings demonstrate that combined determinations of serum and CSF proteins by simple zone electrophoresis and commercial immunochemical tests can be useful laboratory aids in the diagnosis of MS. The MRI scans provide additional evidence to support the diagnosis of MS.

Albumins↗

Depression in opioid users varies with substance use status.

The relation of substance use status to depressed mood during careers of 173 opioid users was estimated using the Zung Self-Rating Depression Scale. The data suggested a progression in severity of depression from those abstinent or using occasionally, who were least depressed, through intermediate substance use states, to those dependent on illicit opioids, who were most depressed. One hundred five subjects completed the Scale in two interviews separated by a mean of 4.5 years. Change in substance use status from not dependent at first interview to dependent at second interview was associated with increased depression.

Adult↗

Cryoglobulinemia in autoimmune rheumatic diseases. Evidence of circulating monoclonal cryoglobulins in patients with primary Sjögren's syndrome.

The incidence and nature of cryoglobulins, as well as their correlation with the clinical and serologic picture of Sjögren's syndrome (SS), were studied in the sera of 30 consecutive primary SS patients. Sera from 29 patients with systemic lupus erythematosus, 58 patients with rheumatoid arthritis, and 125 healthy blood donors were also studied. It was shown that one-third of the patients with SS had cryoglobulinemia. These cryoglobulins were mixed monoclonal IgM immunoglobulins, whereas those observed in systemic lupus erythematosus and rheumatoid arthritis patients were mixed polyclonal. The nature of the cryoglobulins was demonstrated using high-resolution electrophoresis combined with immunofixation. The presence of cryoglobulins in the sera of SS patients correlated with extraglandular disease and with antibodies to Ro (SS-A) and IgM rheumatoid factor. SS patients with cryoglobulins had lower serum C4 levels than did patients without cryoglobulins. These findings suggest that SS expresses, in addition to polyclonal B cell hyperreactivity, a monoclonal process in the absence of lymphoid neoplasia. Further, they show that the extraglandular manifestations of the syndrome may be due to an immune complex-mediated pathology.

Adult↗

Cryoglobulinemia in primary Sjögren's syndrome: a monoclonal process.

Patients with primary Sjögren's syndrome have in their sera and urine free light chains or monoclonal immunoglobulins. In addition, they have mixed monoclonal (IgM kappa) cryoglobulinemia, which is associated with extraglandular disease and greater incidence of autoantibodies. In the present study, it is demonstrated by a high resolution agarose gel electrophoresis, combined with immunofixation, that nine patients with primary Sjögren's syndrome have mixed monoclonal (IgM kappa) cryoglobulins, in contrast to those observed in five patients with secondary Sjögren's syndrome (Sjögren's syndrome and rheumatoid arthritis), 13 patients with rheumatoid arthritis and six patients with systemic lupus erythematosus, which were mixed polyclonal.

Antibodies, Monoclonal↗

Oligoclonal immunoglobulins in patients with the acquired immunodeficiency syndrome.

Analysis of serum samples from patients with the acquired immunodeficiency syndrome (AIDS) was performed by high-resolution zone electrophoresis. A high incidence of monoclonal and oligoclonal immunoglobulins was detected in the sera of 24/27 patients with Kaposi's sarcoma and in 2/15 patients with opportunistic infections. The presence of monoclonal bands was independent of whether or not the patients had experienced an opportunistic infection. These findings indicate a monoclonal or oligoclonal B-cell activation occurring in a much higher frequency in AIDS patients with Kaposi's sarcoma, thus suggesting that similar mechanisms may be operative in the malignant or pseudomalignant proliferation of B-cells and endothelial cells in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

Demonstration and identification of monoclonal proteins in the urine of patients with Sjögren's syndrome.

Fresh sera and concentrated urine from 17 patients with primary Sjögren's syndrome (SS) were fractionated by high-resolution agarose electrophoresis to investigate the presence of monoclonal immunoglobulins or their components. Homogeneous protein bands were found in the gamma-globulin region in 47% of serum samples and 76% of urine specimens of all patients tested. These monoclonal proteins were detected more often in patients with extraglandular SS (77% in serum, 100% in the urine) than in patients with glandular SS (14% in serum, 43% in the urine). Immunofixation electrophoresis showed that the majority of these monoclonal proteins were free kappa or lambda light chains. Fractionation of unconcentrated parotid salivas from five SS patients failed to reveal the presence of monoclonal light chains or immunoglobulins. The present findings further substantiate our previous observation that a monoclonal process coexists with the polyclonal activation in SS patients.

Adult↗

Combined immunochemical and electrophoretic determinations of proteins in paired serum and cerebrospinal fluid samples.

Albumin and immunoglobulin G were simultaneously determined in paired serum and cerebrospinal fluid samples from healthy volunteers. The albumin quotient and the IgG index were calculated to establish normal values. High-resolution electrophoresis was also performed with the same samples and the electrophoretic patterns were correlated with the numerical values to improve the reliability of the test results. Representative examples from abnormal conditions are also shown, to illustrate the increased accuracy and useful applications of this combined analysis in the diagnosis of neurological conditions.

Adult↗

Comparison of netilmicin and gentamicin pharmacokinetics in humans.

In a crossover study, single doses of netilmicin and gentamicin were administered intramuscularly, each at 1.0 and 2.5 mg/kg. The serum concentrations, analyzed by a two-compartment open model with a first-order absorption, indicated that the pharmacokinetics of the drugs are essentially the same. Both drugs were rapidly absorbed and distributed after administration. No significant differences were observed between the two drugs in disposition half-life, rate of distribution and elimination, area under the serum concentration-time curve, urinary excretion, total body clearance, and renal clearance. After 1.0 mg/kg, the maximum serum concentration of netilmicin (5.18 microgram/ml) was only slightly lower than that for gentamicin (5.76 microgram/ml), but no difference was found after the 2.5-mg/kg dose.

Adolescent↗

Comparative nephrotoxicity of aminoglycoside antibiotics in rats.

Netilmicin, gentamicin, tobramycin, amikacin, kanamycin, streptomycin, and sisomicin were given daily for 15 days to groups of rats at three dosage levels corresponding to 10, 15, or 25 times the dose recommended for humans on a weight basis. Decreased urinary osmolality and increased urinary excretion of protein and beta-N-acetyl hexosaminidase were dose-related features of nephrotoxicity. Decreased tubular resorption of glucose and phosphate were observed with the most toxic regimens after extensive renal damage had occurred. All aminoglycosides accumulated in renal tissue; however, the concentration of drug in the renal cortex at the time the rats were killed was not useful for the prediction of renal impairment. Streptomycin and netilmicin exhibited a flat dose-reponse curve with respect to histological damage, as compared with the curves for the other drugs. Results of studies of creatinine clearance and examination of renal tissue suggested the following order of increasing toxicity of the treatment regimens: (1) 0.9% NaCl and uninjected controls; (2) streptomycin; (3) netilmicin; (4) tobramycin; (5) sisomicin, amikacin, and kanamycin; and (6) gentamicin.

Amikacin↗

Measurement of resistance to experimental tuberculosis in albino mice. The immune phase.

Enhanced resistance against experimental tuberculosis was acquired by albino mice after peritoneal vaccination with living BCG. Prolongation of life was used as a measure of resistance against massive intravenous challenge infection. The average degree of prolongation of life was found to be directly related to the size of the vaccinating dose. The ultimate numbers of BCG bacilli recovered from the animal's organs were also directly related to the quantity of vaccine initially administered. It appears therefore that the relative degree of antitubercular resistance achieved by immunized mice is closely related to the vaccinal population present in the animal's organs.

Aerosols↗

Temporal development of resistance to pulmonary tuberculosis in Swiss albino mice.

The course of pulmonary tuberculosis was followed in control and BCG-vaccinated mice. Resistance was evaluated by determining the numbers of virulent mycobacteria recovered from the organs at various intervals after airborn infection. A limited but significant retardation of growth of challenge bacilli was observed in both pulmonary and splenic tissues of successfully vaccinated animals. This retardation was manifested chiefly during the early stages of the infection. However, the numbers of virulent organisms recovered from the organs of either vaccinated or control animals were much the same at later stages of the infection. The appearance of pulmonary immunity was related to the stage of development in vivo of the vaccinal population. Only after large numbers of vaccinal bacilli could be recovered from the tissues was heightened resistance observed.

Aerosols↗

Tuberculous morbidity in Swiss albino mice immunized with BCG.

Study was made of the effect of BCG vaccination on the establishment of experimental tuberculous infection in mice. To this end, mice were infected with small quantities of virulent human bacilli administered by the respiratory route. The quantity of bacilli present for inhalation was so controlled as to permit only a finite percentage of unvaccinated animals to become infected. The relative proportion of mice infected by inhaling these small numbers of virulent bacilli was not found to be lowered by prior BCG vaccination. Thus, pulmonary tissue of immunized mice was not able to prevent the initial lodgement of virulent tubercle bacilli. The growth of virulent organisms in infected lungs, however, was significantly retarded by prior vaccination.

Animals↗