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Biomedical subjects

R A Miller

Publications and source records attributed to R A Miller.

At least 271 records · Page 15Linked to original sources
PubMed1991

Problem area formation as an element of computer aided diagnosis: a comparison of two strategies within quick medical reference (QMR).

INTERNIST-I's use of "partitioning" to group related diagnoses into problem areas (for competitive consideration and elimination during case analysis) is felt to be the source of many of its strengths as well as some of its weaknesses. QMR, INTERNIST-I's successor program, embodies a homology function which can act as an alternative to the partitioner for problem area formation. This study undertakes a comparison of the problem areas generated by the INTERNIST-I partitioning algorithm, the QMR homology function, and expert clinicians; it finds the correlation to be poor. The authors then discuss another method of problem area formation which might better mimic a human clinician and provide an alternative approach in diagnostic computer-aided decision making.

Algorithms↗
PubMed1990

Carcinogenicity of 1,3-butadiene in C57BL/6 x C3H F1 mice at low exposure concentrations.

The carcinogenicity of inhaled 1,3-butadiene was evaluated in C57BL/6 x C3H F1 mice exposed to concentrations of this gas ranging from 6.25 to 625 ppm. Butadiene is a high production volume chemical, used mainly in the manufacture of synthetic rubber. In these 2-yr inhalation studies, a potent multisite carcinogenic response was observed, including neoplasms of the lung at concentrations as low as 6.25 ppm. Early occurrence and extensive development of lethal lymphocytic lymphomas in mice exposed to 625 ppm of butadiene reduced the number of animals at risk for the expression of later developing neoplasms at other sites; at lower exposure concentrations, dose responses were demonstrated for hemangiosarcomas of the heart and neoplasms of the lung, forestomach, Harderian gland, preputial gland, liver, mammary gland, and ovary. So far, no long-term studies on butadiene have been conducted at exposure concentrations that have not shown a carcinogenic response. In separate experiments with reduced exposure durations, butadiene induced neoplastic responses at multiple organ sites even after only 13 wk of exposure. Because of the correspondence between these animal data and recent epidemiology findings, there is a worldwide public health need to reevaluate current workplace exposure standards for 1,3-butadiene.

Animals↗
PubMed1990

Determinants of the antitumor effect of radiolabeled monoclonal antibodies.

The murine B-cell lymphoma 38C13 model was used to study the radiobiological effect of 131I-monoclonal antibody (MAB) therapy compared with dose equivalent external beam irradiation. Continuous exponentially decreasing low dose rate (LDR) gamma-irradiation, and multiply fractionated (MF) X-irradiation were compared with dose equivalent 131I-MAB. The relative therapeutic efficacy of radioimmunotherapy, and the relative contribution of (a) low dose rate; (b) whole body irradiation; and (c) microdosimetry to the overall effect were determined. Groups of mice with or without B-cell lymphoma were treated with either (a) 131I-anti-idiotype MAB; (b) 131I-isotype-matched irrelevant control MAB; (c) 5-15 Gy 250 kV X-irradiation given as a single fraction; (d) 2.5-30 Gy 250 kV X-irradiation given in 10 fractions/2 weeks; or by (e) continuous exponentially decreasing gamma-irradiation via a 137Cs source, which simulated the effective t1/2 of the 131I-MAB. In tumor-free mice the LD50/30 was approximately 10 Gy for MF and LDR external irradiation, and 11-12 Gy for 131I-MAB. However, the effect of these modes of irradiation on tumor size differed significantly. The cumulative percentage of tumor reduction averaged over 12 days was 0.635 +/- 0.055%/Gy for MF, and 1.36 +/- 0.061%/Gy for LDR external irradiation (a relative efficacy factor of 1.63 for LDR irradiation; P = 0.01). Assuming homogeneous body distribution, the tumor reduction effect over 12 days for 131I-MAB was 2.064 +/- 0.133%/Gy for specific, and 1.742 +/- 0.1%/Gy for nonspecific isotype-matched irrelevant 131I-MAB (P = 0.02). When 131I-MAB was compared to LDR external irradiation, the relative efficacy factor was 1.99 (P less than 0.001). In summary, there was a dose rate effect on tumor response, which may in part explain the efficacy of radioimmunotherapy. The additional effect of 131I-MAB on tumor response was only partially explained by the cumulative concentration ratio of 131I-MAB tumor/131I-MAB whole body, which was on average 1.7. This relatively low concentration ratio was partly due to tumor-mediated dehalogenation. Thus, the overall tumor response was a function of the total dose, dose rate, and both the specific and nonspecific distribution of 131I-MAB.

Animals↗
PubMed1990

Expression of shared idiotypes by paraproteins from patients with multiple myeloma and monoclonal gammopathy of undetermined significance.

Twenty-nine murine monoclonal antibodies have been produced that react with shared idiotypes expressed by B-cell lymphomas and leukemias. We tested this panel of antibodies for reactivity with the paraproteins from 32 patients with multiple myeloma and 10 patients with monoclonal gammopathy of undetermined significance (MGUS). Thirteen of 42 paraproteins reacted with at least one antibody in this panel of anti-idiotypic antibodies. Six different anti-idiotypes demonstrated reactivity with the paraproteins. A similar frequency of reactivity was found for both myeloma and MGUS proteins. One antibody, S30-47, reacted with 6 of 32 (19%) of the paraproteins from patients with multiple myeloma, whereas this anti-idiotype only bound to 3% of non-Hodgkin's B-cell lymphomas and no cases of chronic lymphocytic leukemia. This anti-idiotype reacted with both components of a biphenotypic paraprotein (IgG kappa and IgG lambda) in one patient. In each of nine patients tested, plasma cells isolated from bone marrow were shown to be reactive with the same anti-idiotype we found to react with the paraprotein. Antishared idiotype antibodies may provide useful reagents for studies of patients with monoclonal gammopathies.

B-Lymphocytes↗
PubMed1990

Radioimmunotherapy of human B-cell lymphoma with 90Y-conjugated antiidiotype monoclonal antibody.

We report the first case of 90Y-conjugated monoclonal antibody (MoAb) administration for human radioimmunotherapy. Ten mCi 90Y-labeled antiidiotype (anti-Id) MoAb were administered to a patient with B-cell lymphoma whose tumor successfully imaged with 111In-labeled anti-Id MoAb. No significant toxicities were observed. More than 2 g of unlabeled anti-Id MoAb were administered while clearing the circulating IgM idiotype prior to administration of the 90Y-MoAb. Transient partial regression of disease was observed. Serial fine needle aspirations of a malignant lymph node documented in vivo anti-Id penetration into a site that did not image by radioimmunoscintigraphy. The radiosensitivity of B-cell lymphoma, the tumor specificity of anti-Id, the antitumor activity of anti-Id alone, and the safe administration of 10 mCi 90Y-labeled anti-Id MoAb in this report suggest further investigation of this radioimmunoconjugate for therapy of B-cell lymphoma is warranted.

Adult↗
PubMed1990

Leishmania gp63 molecule implicated in cellular adhesion lacks an Arg-Gly-Asp sequence.

The parasitic protozoa Leishmania are intracellular pathogens which enter host cells through largely undefined mechanisms. One molecule thought to play an important role in this process is gp63, the major glycoprotein on the surface of the infective promastigote form. We have cloned and analyzed the gp63 gene from Leishmania chagasi, an etiologic agent of acute visceral leishmaniasis. The predicted amino acid sequence is highly homologous to that reported for Leishmania major, with the exception of a 56-amino-acid region. This region in L. major was predicted to contain an arginine-glycine-aspartic acid (RGD) sequence that was subsequently hypothesized to be involved in binding to the host cell. The L. chagasi gene lacks this sequence or indeed any RGD sequence, and further studies failed to confirm the existence of an RGD sequence in the L. major gp63 gene. Binding to the host cell surface must therefore be mediated by other sequences in gp63 or by other components of the Leishmania promastigote.

Amino Acid Sequence↗
PubMed1990

Radioactive gold ring dermatitis.

A superficial squamous cell carcinoma developed in a woman who wore a radioactive gold ring for more than 30 years. Only part of the ring was radioactive. Radiation dose measurements indicated that the dose to basal skin layer was 2.4 Gy (240 rad) per week. If it is assumed that the woman continually wore her wedding ring for 37 years since purchase, she would have received a maximum dose of approximately 4600 Gy.

Carcinoma, Squamous Cell↗
PubMed1990

Subchronic toxicity of tetrahydrofuran vapors in rats and mice.

Tetrahydrofuran (THF), a four-carbon, cyclic ether, is widely used as an industrial solvent. Groups of 10 rats and mice of each sex were administered THF vapor by whole body inhalation for 13 weeks at exposure concentrations of 0, 66, 200, 600, 1800, and 5000 ppm. The body weights and survival were not affected by THF exposure, except in male mice at 5000 ppm concentration which had reduced weight and three deaths. Clinical signs of central nervous system (CNS) toxicity were observed in both rats and mice at high dose levels. Rats of both sexes exposed to 5000 ppm were ataxic and mice exposed to 1800 or 5000 ppm appeared to be in a state of narcosis. There were no exposure-related gross necropsy findings in rats or mice. At 5000 ppm, decreases in thymic and spleen weights in rats and mice of both sexes and increases in liver weights in both sexes of mice and in female rats were observed. A minimal to mild centrilobular hepatocytomegaly occurred in male and female mice exposed to 5000 ppm THF. Atrophy of the uterus and degeneration of the X zone in the adrenal cortex occurred in female mice exposed to 5000 ppm THF. THF exposure of rats was associated with minimal to mild acanthosis and inflammation in the forestomach. In conclusion, these studies suggest that THF, like other commonly used organic solvents, causes narcosis in rats and mice. Although minimal exposure-related effects were seen in the liver of both species, morphologic changes were present only in mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1990

Rabies reference vaccine for use as a regional standard for Latin America and the Caribbean countries.

A candidate rabies reference vaccine of suckling mouse brain (SMB) origin was prepared and standardized at the Pan American Zoonoses Center (PAHO/WHO) and evaluated in a collaborative study involving seven laboratories. On the basis of three different tests, its potency, immunogenicity, and stability were demonstrated to be satisfactory. The vaccine was proposed for consideration of the Latin American and Caribbean countries as a regional standard to determine the potency of SMB vaccines, the most widely used in the Region.

Animals↗
PubMed1990

Diels-Alder adducts of vinyl porphyrins: synthesis and in vivo photodynamic effect against a rat bladder tumor.

Benzoporphyrin derivatives have been proposed as potential photosensitizers for photodynamic therapy. We have prepared a number of benzoporphyrin derivatives and tested their effect, in combination with red light, on the N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) induced rat bladder tumor (AY-27) transplanted into Fischer CDF(F344)/CrlBr rats. Tetracyanoethylene (TCNE) adducts showed very little activity, which may be attributable to their poor tumor uptake or to chemical instability of the adduct under physiological conditions. However, dimethyl acetylenedicarboxylate (DMAD) adducts tested showed greater cytotoxic effect than hematoporphyrin derivative and similar activities to metallopurpurins when tested under the same protocol.

Acetylene↗
PubMed1990

Vitamin E supplementation enhances cell-mediated immunity in healthy elderly subjects.

The effect of vitamin E supplementation on the immune response of healthy older adults was studied in a double-blind, placebo-controlled trial. Subjects (n = 32) resided in a metabolic research unit and received placebo or vitamin E (800 mg dl-alpha-tocopheryl acetate) for 30 d. Alpha-tocopherol content of plasma and peripheral blood mononuclear cells (PBMCs), delayed-type hypersensitivity skin test (DTH), mitogen-stimulated lymphocyte proliferation, as well as interleukin (IL)-1, IL-2, prostaglandin (PG) E2, and serum lipid peroxides were evaluated before and after treatment. In the vitamin E-supplemented group 1) alpha-tocopherol content was significantly higher (p less than 0.0001) in plasma and PBMCs, 2) cumulative diameter and number of positive antigen responses in DTH response were elevated (p less than 0.05), 3) IL-2 production and mitogenic response to optimal doses of concanavalin A were increased (p less than 0.05), and 4) PGE2 synthesis by PBMCs (p less than 0.005) and plasma lipid peroxides (p less than 0.001) were reduced. Short-term vitamin E supplementation improves immune responsiveness in healthy elderly individuals; this effect appears to be mediated by a decrease in PGE2 and/or other lipid-peroxidation products.

Aged↗
PubMed1990

Diminished calcium signal generation in subsets of T lymphocytes that predominate in old mice.

We have recently demonstrated an age-dependent increase in the fraction of murine T cells that express high levels of the Pgp-1 surface glycoprotein, thought to be a marker for memory lymphocytes. T cells from old mice also exhibit a defect in the generation of cytoplasmic calcium signals after stimulation with Con A. To see if the increase in Pgp-1+ T cells could account for defective calcium signal generation in old mice, we carried out flow cytometric analyses to examine calcium signal production in T cells expressing high or low levels of the Pgp-1 marker. We report here that Pgp-1+ T cells, from both old and young mice, do indeed generate relatively poor Ca2+ responses when exposed either to receptor-dependent mitogens (e.g., Con A and anti-CD3) or to activators like ionomycin that bypass receptor-mediated signal transduction pathways. Both CD4 (helper) and CD8 (killer) T cells show poor calcium responses. These data suggest that the shift, with age, toward Pgp-1+ T cells, which are relatively refractory to stimuli that raise intracellular calcium concentrations, may contribute to poor cell-mediated immune function in old animals.

Aging↗
PubMed1990

Experimental cryptosporidiosis in a primate model.

Cryptosporidium causes a disease in infant macaques that is clinically, histologically, and microbiologically indistinguishable from that seen in young children. A reproducible experimental model of cryptosporidiosis has been developed in pigtailed macaques (Macaca nemestrina) and used to studied the infectious dose of oocysts and the effect of inoculum size on severity of disease. Inoculation with either 2 x 10(5) or 10 oocysts via nasogastric tube resulted in clinical enteritis and the fecal passage of large numbers of cryptosporidial oocysts in all four primates studied. The size of the inoculum had no apparent effect on the severity or duration of disease. Rechallenge 2 weeks after resolution of the primary infection demonstrated partial acquired immunity. The small inoculum size coupled with the passage of large numbers of oocysts contributes to the highly contagious nature of cryptosporidiosis among captive primates and may be relevant to the epidemiology and control of cryptosporidiosis in humans.

Animals↗
PubMed1990

Why the standard view is standard: people, not machines, understand patients' problems.

The 'Standard View' regarding computer-based medical diagnostic decision support programs is that, while such systems may be useful adjuncts to human decision-making, they cannot replace human diagnosticians. Mazoué (1990) disputes this viewpoint. He notes that human diagnosis is prone to a variety of errors, and claims that the processes of data collection for diagnosis and the intellectual task of making a diagnosis are independent. Mazoué believes that recent progress in computer-based diagnosis has been encouraging enough to consider the concept of "human-assisted computer diagnosis". This commentary explains why the Standard View should remain standard. Diagnosis is a complex process more involved than producing a nosological label for a set of patient descriptors. Efficient and ethical diagnostic evaluation requires a broad knowledge of people and of disease states. The state of the art in computer-based medical diagnosis does not support the optimistic claim that people can now be replaced by more reliable diagnostic programs.

Attitude to Computers↗
PubMed1990

Biliary manometry.

The purpose of the paper is to introduce the reader to sphincter of Oddi dysfunction and the technique of biliary manometry. This paper will review sphincter of Oddi anatomy and physiology, abnormalities, patient selection, equipment and technique used in testing, interpretation and scoring.

Cholangiopancreatography, Endoscopic Retrograde↗