Comparison of the Gene-Tox and RTECS data bases as predictors of carcinogenic potency.
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Carcinogenicity Tests↗
Biomedical subjects
J M Morris
Publications and source records attributed to J M Morris.
On the use of 0.75 as an interspecies scaling factor.
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Animals↗
Sonographic evaluation of intrauterine growth retardation.
The prenatal recognition of the growth-retarded fetus is important because of the associated increased perinatal morbidity. Clinical methods of assessing fetal growth are disappointing and necessitate that a high-risk group be identified for more intensive surveillance. This review discusses the role of ultrasound biometry in establishing whether a fetus is small. Behavioral characteristics of the fetus may also be assessed using real-time ultrasound. The realization that not all small fetuses are a result of growth failure has led to the development of Doppler ultrasound to identify the fetus at risk. This paper focuses on the evidence supporting the selected use of Doppler ultrasound to investigate high-risk pregnancy.
Female↗
Membranoproliferative glomerulonephritis in dogs with a genetically determined deficiency of the third component of complement.
Renal disease is a common clinical manifestation of genetically determined deficiencies of the complement system in man. Like their human counterparts, dogs with a genetically determined complete deficiency of C3 also develop renal disease. Five of 20 C3-deficient dogs developed clinical evidence of renal failure. However, 14 of the 15 remaining dogs had histological evidence of type I membranoproliferative glomerulonephritis. The lesions were characterized by mesangial cell proliferation, an increase in the mesangial matrix, thickening of the glomerular capillary wall, electron-dense deposits in the mesangium and subendothelial space, and the presence of IgG and IgM. In order to determine the effect of treatment with C3 on the renal disease of C3-deficient dogs, two C3-deficient dogs were infused with normal canine plasma twice weekly for 3 weeks. Their urinary protein excretion rose progressively from less than 200 mg/24 hr to greater than 1000 mg/24 hr; renal function remained normal. Renal biopsies performed 1 week after the last infusion revealed more severe glomerulonephritis and the presence of C3. As controls, a C3-deficient dog was given C3-deficient canine plasma and a normal dog was given normal canine plasma; neither control animal developed proteinuria or changes in their renal biopsy. These observations suggest that renal disease may be more common in humans with complement deficiencies than would be suspected based on clinical assessment. Furthermore, these results suggest that treatment with complement-containing blood products may worsen preexisting renal disease in complement-deficient individuals.
Animals↗
Pancreatic adenocarcinoma with osseous metaplasia in a ferret.
A poorly differentiated pancreatic adenocarcinoma with regional lymphatic, hepatic, enteric and pulmonary metastases was diagnosed in an adult European ferret (Mustela putoris furo). The ferret showed clinical signs including a progressive, marked abdominal enlargement owing to ascites. Microscopic findings included intralesional osseous metaplasia. Exocrine pancreatic neoplasms in ferrets are rarely reported compared with neoplasms with endocrine differentiation.
Adenocarcinoma↗
Lumbar spinal fusion. Assessment of functional stability with magnetic resonance imaging.
Segmental spinal instability was evaluated with magnetic resonance (MR) imaging, computed tomography (CT), and conventional radiography in 33 patients who had undergone surgical spinal fusion. In 16 of the 19 patients who had a diagnosis of solid fusion, the immobilized vertebral bodies demonstrated areas of high signal intensity on images with short repetition time (TR) and echo time (TE). The signal intensity of these areas was either less intense or normal on images with long TR and TE. In 10 of the 14 patients with segmental instability at the fusion site, subchondral vertebral bands of low signal intensity were shown on short TR/TE images, which demonstrated high signal intensity on long TR/TE images. All but two of the patients showed vertebral signal changes 12 or more months past fusion or onset of clinical symptoms. The vertebral MR signal intensity in solid lumbar fusions might be related to marrow composition changes resulting from decreased biomechanical stress, while the vertebral signal intensities in patients with unstable fusions might be related to reparative granulation tissue, inflammation, edema, and hyperemic changes. Magnetic resonance imaging appears to be unique in its assessment of functional fusion stability. Magnetic resonance may be most useful in patients symptomatic of fusion pseudarthrosis in whom conventional radiography and CT fail to demonstrate anatomic disruption.
Female↗
Changes in neuronal size and neurotransmitter marker in hereditary canine spinal muscular atrophy.
Hereditary canine spinal muscular atrophy (HCSMA) is a dominantly inherited motor neuron disease that produces muscle weakness and atrophy. Immunocytochemical and computer-imaging morphometric methods were used to compare early changes that occurred in dogs with HCSMA (n = 4) versus controls (n = 2). The size and number of neurons in the ventral horn and the number of motor neurons expressing choline acetyltransferase were quantitated. The density of all ventral horn neurons per micrometer squared in dogs with HCSMA was greater than controls, and there were more small neurons than in controls. Immunocytochemical methods revealed more small cholinergic neurons and fewer large cholinergic neurons in HCSMA than in controls, suggesting growth arrest in HCSMA or a shift in size class from large cholinergic neurons to small ones. The density of cholinergic neurons per micrometer squared was not significantly different between the two groups. Analysis of predicted distributions of cholinergic and noncholinergic neurons revealed that HCSMA cholinergic neurons were smaller and that, in some size classes, fewer neurons expressed choline acetyltransferase. These observations indicate that in HCSMA the motor neuron fails to achieve normal size and/or undergoes atrophy.
Animals↗
Role of C3 in humoral immunity. Defective antibody production in C3-deficient dogs.
Previous studies have shown that animals pharmacologically depleted of C3 have impaired antibody responses. However, such C depletion is neither complete nor sustained, and the C3 cleavage products generated by C3 depletion can both enhance and inhibit the immune response. To clarify the role of C3 in humoral immunity, the antibody response of dogs with genetically determined total deficiency of C3 (C3D) was examined. Serum IgG levels of the C3D animals were within the normal range, but were significantly lower than levels seen in normal controls or C3D heterozygotes. Specific antibody production was defective: the antibody titers of C3D dogs in response to primary intravenous immunization with two different T cell-dependent Ag (sheep E and bacteriophage phi X-174) were markedly reduced when compared to either normal controls or C3D heterozygotes. After secondary immunization with T-dependent Ag, the total antibody titers were normal, but the C3D dogs made proportionately more IgM and less IgG antibody than did either control group. After i.v. immunization with a T cell-independent Ag (DNP-Ficoll), the C3D dogs had reduced levels of IgM and IgG antibody after primary and secondary immunization. Neither i.m. immunization nor the use of a 20-fold increase in Ag dose i.v. could correct the defect seen in the antibody response of C3D dogs. The results herein demonstrate that C3 plays a critical role in the generation of a normal humoral immune response.
Agammaglobulinemia↗
Association of seminal desethylamiodarone concentration and epididymitis with amiodarone treatment.
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Adult↗
[3-dimensional computed tomography and multiplanar CT-reformations in lumbar spondylodesis].
Three-dimensional computed tomography (3-D-CT) and multiplanar CT reformations were performed in 42 patients who were clinically suspected of spinal instability following posterior lumbar fusion. Sagittal and coronal CT reformations demonstrated fusion pseudarthrosis more frequently than axial CT or conventional radiography. Three-dimensional CT cuts through the fusion revealed pseudarthrosis in most patients with positive 2-D images. In 5 patients, however, fusion appeared to be artifactually stable or unstable on 3-D cuts contrasting the 2-D images. Three-dimensional surface reconstructions demonstrated the complex anatomy of the fusion and showed superficial breaks. They were helpful in preoperative planning as well as intraoperative localization. 3-D-CT is a clinically useful adjunctive imaging method.
Adult↗
Three-dimensional computed tomography and multiplanar reformations in the assessment of pseudarthrosis in posterior lumbar fusion patients.
Three-dimensional (3-D) surface reconstructions and multiplanar computed tomography (CT) reformations were obtained in 30 patients with clinically suspected spinal fusion pseudarthrosis. The imaging studies were blind-reviewed and the results were compared with the clinical and surgical findings. Sagittal, planar, and curved coronal two-dimensional (2-D) reformations were more useful in the detection of bony nonunion than were axial CT scans, as the latter required more extensive analysis. Three-dimensional surface "cuts" adequately demonstrated pseudarthrosis in most cases. In some instances, however, segmentation artifacts created artifactual clefts or implied solidity, which contrasted with the interpretation of the 2-D images. Sagittal 3-D cuts were helpful in demonstrating bony central and lateral stenosis. Three-dimensional surface reconstructions demonstrated superficial clefts and outlined the complex anatomy of the spinal fusions, thus facilitating pre- and intraoperative planning. The amount of bone stock available for pseudarthrosis repair at the fusion site and the need for additional harvesting of bone from the iliac crest also could be assessed easily. 3-D CT proved to be useful as an adjunctive imaging method in the evaluation of posterior lumbar fusion patients suspected of pseudarthrosis.
Adult↗
Serum lactic dehydrogenase: a tumor marker for dysgerminoma.
Four patients with stage IA-IIIC dysgerminomas were found to have preoperative elevations of serum lactic dehydrogenase (LDH) 1.8-51.5 times that of the upper limits of normal control values, in association with minor elevations of liver function tests (alkaline phosphatase, serum glutamic oxaloacetic transaminase, and serum glutamic pyruvic transaminase) up to 2.5 times normal control limits. Recognition of the association between this serum enzyme profile and dysgerminoma resulted in proper intraoperative staging and prompt initiation of chemotherapy in two patients. Failure to recognize the significance of the serum enzyme profile resulted in inadequate intraoperative staging and reoperation in one of the remaining patients. Serum LDH levels correlated with tumor size and stage of disease. Maximum tumor diameters in this series varied from 15-20 cm. A normal LDH level was present in an intraoperative serum sample obtained from a stage IA patient whose maximum tumor diameter was 8 cm. Selective elevation of LDH-1 and LDH-2 isoenzymes may provide additional evidence suggesting the presence of a dysgerminoma.
Adolescent↗
Pseudarthrosis following lumbar fusion: detection by direct coronal CT scanning.
Twenty patients with fusions of the lumbar spine (seven with pseudarthrosis, 11 with solid bony fusions, and two with fusions that appeared solid but assessment was complicated by the presence of surgical hardware) underwent computed tomographic (CT) scanning in the supine position in the axial plane and, employing a specially designed seat, in the coronal plane. Three-millimeter contiguous sections were acquired. The direct coronal images were compared with those reformated from the axial images. The higher-resolution direct coronal images facilitated the diagnosis of pseudarthrosis and increased confidence in interpretation of normal studies. Direct coronal imaging is easy to perform and in many cases requires fewer scans and less radiation than reformations. Because it provides more useful diagnostic information, direct coronal imaging should replace current methods for evaluating fusions of the lumbar spine.
Adult↗
Anaphylactic and anaphylactoid reactions. A review.
Anaphylaxis is a life-threatening, immunologically mediated reaction. "Anaphylactoid" reactions produce the same clinical syndrome but are not immunologically mediated. Vasoactive mediators of these reactions include histamine, eosinophilic chemotactic factors of anaphylaxis, slow reacting substance of anaphylaxis (a mixture of three leukotrienes, one a potent coronary vasoconstrictor), kinins, and prostaglandins. Symptoms usually occur within 15 minutes of parenteral injection of the causative agent, but can be delayed as long as 2.5 hours. Because vasodilation occurs at the capillary and postcapillary venule, resulting in loss of fluid and colloid (and hence reduction in effective plasma volume), and then shock, volume replacement is a mainstay of therapy. This article reviews the pathophysiology, incidence, and drug causes of anaphylactic/anaphylactoid reactions and proposes therapy to minimize the consequences of reactions seen by physicians treating spinal conditions.
Anaphylaxis↗
Papillary-annular continuity and left ventricular systolic function after mitral valve replacement.
The contribution of the subvalvular apparatus to left ventricular function was evaluated in a canine preparation that allowed variation of subvalvular tethering forces after mitral valve replacement. Ten normal dogs were instrumented with micromanometer-tipped pressure catheters in the left ventricle and left atrium and piezoelectric sonomicrometry crystals to measure left ventricular major-axis, minor-axis, and wall thickness dimension changes. After control data were obtained, each dog underwent cardiopulmonary bypass and the mitral valve was replaced with a St. Jude bileaflet valve (No. 23 or 25). The native valve was completely excised and all chordal attachments were severed at the head of each papillary muscle. A 3-0 prolene suture was passed through the head of each papillary muscle, gently tied over a pair of felt pledgets, and exteriorized in a paravalvular manner that allowed both "attached" and "detached" states to be studied in a randomized manner 1 hr after release of the aortic cross-clamp. A significant (p less than .05) increase in major-axis length from control was observed in the detached state at both end-diastole and end-systole when compared at matched left ventricular end-diastolic pressures. Systolic function measured by load-dependent variables at matched end-diastolic lengths was higher in the detached state. However, when systolic function was examined by load-independent variables such as the slope of the stroke work end-diastolic length relationship, the slope of the end-systolic pressure-volume relationship, or the stroke work end-diastolic volume relationship, no statistically significant difference could be detected between states of papillary-annular continuity.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Partial characterization of solubilized platelet imipramine binding sites using a new probe, [3H]3-cyanoimipramine ([3H]Ro 11-2465).
Evidence suggests that [3H]imipramine labels the recognition site of the neuronal 5-hydroxytryptamine uptake mechanism. We are investigating the linkage between these binding sites and the carrier by biochemical characterization. [3H]Imipramine-labelled sites have been solubilized from outdated human platelets using the detergent digitonin. [3H]3-Cyanoimipramine binds persistently to these sites in the presence of Na+ at 4 degrees C. At higher temperatures, and in the absence of Na+, this ligand acts reversibly. We report the use of this pseudo-irreversible ligand in the initial molecular characterization of the recognition molecule. To confirm that this ligand occupies the [3H]imipramine-labelled sites, human platelets were prelabelled with 3-cyanoimipramine before incubating with [3H]imipramine. Only low affinity [3H]imipramine binding remained. The majority of the 3-cyanoimipramine was irreversibly bound under these conditions as shown by the use of the 3H compound. Gel permeation chromatography of [3H]3-cyanoimipramine-prelabelled platelet membranes solubilized with digitonin indicated a Stokes' radius of 6.3 nm. This is larger than values previously determined for cholate-solubilized sites. We conclude that [3H]3-cyanoimipramine will be useful for further purification and reconstitution studies.
Binding, Competitive↗