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Biomedical subjects

R E Anderson

Publications and source records attributed to R E Anderson.

At least 217 records · Page 12Linked to original sources

The autopsy and health statistics.

The current state of death statistics in the United States would constitute a national embarrassment if it were not for the fact that the rest of the world seems to be similarly afflicted. This ubiquity of the issue does not, however, make it any less urgent. The etiology of the problem is multifaceted, and remediation will require a broad approach, designed to reach all of the several involved groups of people. The key to the solution, however, is accurate data on the underlying cause of death and contributory diseases, data generally best available through autopsy. More autopsies, more accurate autopsies, and more attention to proper completion of death certificates are needed.

Autopsy↗

National Pathology Manpower Survey of 1988. Manpower needs in community hospitals and private laboratory practice.

The survey of manpower in community hospital and private laboratory practice of pathology of 1988 presented herein verifies the conclusions of the 1986 survey that a growing deficit of manpower in this sphere of practice is highly likely in the next few years. It appears that the deficit will be even larger than that predicted by the 1986 survey. Steps are urgently needed to increase the flow of graduating medical students, especially those of top quality, into our specialty.

Adult↗

Targeting AIDS prevention and treatment toward HIV-1-infected persons. The concept of early intervention.

We propose establishing private and public outpatient facilities where persons with human immunodeficiency virus, type 1 (HIV-1), infection can receive state-of-the-art clinical and behavioral follow-up, treatment, and assistance. The possible advantages of enrolling HIV-1-positive persons into long-term follow-up are early treatment of clinical conditions and resulting gains in life quality and life expectancy, decreased transmission of HIV-1 to uninfected persons, more efficient use of scarce patient-care resources, and improved estimates of the total number of HIV-infected persons. The possible disadvantages of such a program are adverse psychological reactions to knowledge of HIV-1 infection, adverse societal actions against infected persons, and, finally, the economic cost of the program. These facilities, with the proper expertise and safeguards of confidentiality and trust, could prolong and improve the lives of infected persons while preventing infection of others.

AIDS Serodiagnosis↗

Localization of hematoporphyrin. Derivative to human colorectal cancer.

This study documents the affinity of hematoporphyrin derivative (HpD) for human colorectal cancer by analysis of surface fluorescence. Ten patients undergoing elective surgery for primary colorectal cancer received intravenous HpD (2-5 mg/kg) either 3 or 72 hours preoperatively. Fluorescent photographs were taken of freshly resected specimens and analyzed using a computerized videodensitometric technique. This technique subtracted contaminating non-HpD fluorescence and facilitated estimation of HpD tissue levels. The HpD-specific fluorescence localized to tumors in all cases, and the mean HpD concentration was six-fold greater in malignant tissue than in surrounding normal mucosa (0.6 microgram/g versus 0.1 microgram/g, P less than 0.001). The authors conclude that HpD preferentially localizes to human colorectal cancer and this is relevant to the photodetection and phototherapy of colorectal neoplasia.

Adult↗

A model of the pathophysiology of cerebral arteriovenous malformations by a carotid-jugular fistula in the rat.

A model of a carotid-jugular fistula in the rat was created such that the arterial feeding vessel is derived from the intracranial arterial circulation and the venous drainage communicates with a major intracranial venous drainage system. This fistula was created in 28 rats on the right side with an additional 11 rats designed as controls with a right carotid ligation and 6 rats without previous surgery. After 12 weeks convalescence, 6 rats with a carotid-jugular fistula and 6 rats without previous surgery underwent cerebral angiography. All fistulae were patent and the model was verified. All of the 33 remaining rats underwent regional cerebral blood flow (rCBF) determination by [14C]iodoantipyrine autoradiography under barbiturate anesthesia. Of the rats with the fistula, 11 had this fistula obliterated 5 min prior to rCBF determination ('closed' group) while 11 had rCBFs determined with the fistula ('open' group). The rCBF was measured from each hemisphere from 7 anatomical regions. The rCBF in the control animals ranged from a median of 82 to 112 ml/100 g/min, in the 'open fistula' group 46 to 68 ml/100 g/min, and in the 'closed' group 118 to 187 ml/100 g/min. This experimental model stimulates the pathophysiologic perturbations in the parenchyma induced by cerebral arteriovenous malformations. It supports the findings that non-infarctional hypoperfusion can result from arteriovenous malformations and that following extirpation of arteriovenous malformations hyperemia may ensue.

Animals↗

The sensitivity and specificity of clinical diagnostics during five decades. Toward an understanding of necessary fallibility.

Published studies encompassing more than 50,000 autopsies were assessed to determine the sensitivity and specificity of clinical diagnostics (the diagnostic process) in persons dying of 1 of 11 specific diseases during the period 1930 through 1977. The accuracy of clinical diagnostics, as reflected in these two determinations, appeared to improve over this period with respect to some of the diseases studied (rheumatic heart disease and leukemia), while for others it worsened (pulmonary tuberculosis, peritonitis, carcinoma of the lung, gastric carcinoma, and carcinoma of the liver and extrahepatic biliary tract) and for a significant number diagnostic accuracy seemed refractory to sustained change (pulmonary embolism, primary cirrhosis of the liver, gastric/peptic ulcer, and acute coronary thrombosis/myocardial infarction). The findings suggest a new way in which the autopsy can be used to monitor clinical diagnostics to identify possible sources of systematic weaknesses and provide data that can be used to approach the difficult subject of necessary fallibility.

Autopsy↗

Magnetic resonance imaging versus computed tomography--which one?

Both magnetic resonance imaging (MRI) and x-ray computed tomography (CT) are essential diagnostic imaging tools in current practice. The main goal of this article is to provide a quick reference guide to help the busy clinician choose which test to obtain first to avoid the need for a second expensive imaging examination. In general, MRI is preferred for examination of the CNS, the spine for disk disease, major joints, and soft tissues of the extremities. CT is preferred for examination of the head and spine after acute trauma and of the chest, abdomen, and pelvis.

Bone Diseases↗

Mechanism of vitamin A movement between rod outer segments, interphotoreceptor retinoid-binding protein, and liposomes.

Vitamin A movement between rod outer segment (ROS) membranes, interphotoreceptor retinoid-binding protein (IRBP), and liposomes was examined by two different methods. Equilibrium exchange of all-trans-retinol was followed by assessing the transfer of [3H]retinol from liposomes to ROS membranes as compared to a nontransferable marker, [14C]triolein. In the absence of IRBP, a rapid, spontaneous transfer of [3H] retinol to the ROS membranes occurred. In the presence of 2 microM IRBP, retinol transfer decreased by approximately one-half, whereas a similar concentration of bovine serum albumin had no effect on this spontaneous transfer. Kinetics of retinol transfer between single unilamellar vesicles were determined by the method of fluorescence energy transfer. The first order rate constant for this transfer was 0.85 s-1 at 22 degrees C at either pH 7.4 or pH 2.8. This rate was not affected by varying the concentration of acceptor vesicles 50-fold or by varying their concentration 10-fold at a constant ratio of donor-to-acceptor vesicles. The presence of IRBP as an additional acceptor did not change the rate. The transfer was temperature-dependent with an activation energy of 7.8 kcal/mol. The transfer rate appeared to be an increasing exponential function of ionic strength since high concentrations of NaCl decreased the transfer rate significantly. The transfer rate of retinol from IRBP to single unilamellar vesicles also followed first order kinetics with a rate constant of 0.11 s-1 at 22 degrees C, which was approximately 8 times slower than that of transfer between vesicles. We conclude that the transfer of all-trans-retinol between liposomes and membranes can be accomplished rapidly via the aqueous phase, and that IRBP retards rather than facilitates this transfer process.

Animals↗

Spontaneously resorbing ectopic pregnancy: preservation of human chorionic gonadotropin bioactivity despite declining steroid hormone levels.

We compared serum hormone profiles of patients with normal intrauterine pregnancies (n = 14), spontaneously resorbing ectopic pregnancies (n = 10), and viable ectopic pregnancies (n = 26). Hormone profiles were evaluated at 5 to 8 weeks' gestational age. Ectopic pregnancies were diagnosed by laparoscopy; intrauterine gestations were confirmed by ultrasonography. Immunoreactive beta-human chorionic gonadotropin, progesterone, estradiol, and 17-hydroxyprogesterone were measured by radioimmunoassay. Bioactive human chorionic gonadotropin was measured by a modified mouse Leydig cell bioassay. Diminished steroid production was noted in ectopic pregnancies; levels in serum of patients with resorbing ectopic pregnancies were lower than values expressed in viable ectopic pregnancies (p less than 0.01). Serum levels of human chorionic gonadotropin bioactivity correlated closely with immunoreactive human chorionic gonadotropin in all three groups (r = 0.81, p less than 0.01). Ratios of bioactive human chorionic gonadotropin to immunoreactive beta-human chorionic gonadotropin were similar (0.93 +/- 0.26 in resorbing ectopic pregnancies, 1.11 +/- 0.16 in viable ectopic pregnancies, and 0.90 +/- 0.10 in intrauterine pregnancies). We conclude that although reduced serum levels of steroids noted in ectopic pregnancy suggest an impairment in corpus luteum activity, diminished steroid production was not attributable to lower human chorionic gonadotropin bioactivity.

17-alpha-Hydroxyprogesterone↗

Binding of radiolabeled estrogens by human cells in vitro: implications to the development of a new diagnostic and therapeutic modality in the treatment of malignancies with estrogen receptors.

An in vitro technique was employed to demonstrate the binding of Auger electron-emitting nuclide-labeled estrogenic compounds by a variety of human cell types. Human granulosa cells, endometrium, and MCF-7 breast cancer cells were incubated with either 16 alpha-[I125]-iodoestradiol-17 beta or 16 alpha-[I123]-iodoestradiol-17 beta in vitro. Autoradiographic techniques were subsequently utilized and revealed that binding of these estrogenic compounds by all three types of cells did occur and that this binding was inhibited by excess unlabeled estradiol. Histologic examination was not able to demonstrate nuclear-specific binding in all instances, however. These compounds are potentially useful in both diagnostic and therapeutic settings and this study is the first to provide such data from human tissue.

Autoradiography↗

Quantitative morphology of late renal radiation injury.

Late radiation injury manifests itself in all morphologic compartments of the kidney, but loss of cell mass is most significant in the proximal convoluted tubules. Development of an end stage or nonfunctional kidney requires 12 or more months after single fraction X ray exposures of about 12 Gy (2, 5, 13) and is associated with marked morphologic alterations of renal tubules. Radiation induced changes were studied at 6 months after irradiation, a time interval when histological alterations appear minor, but in previous studies were shown to correlate with the later end stage alterations (5, 8, 9). Renal alterations were graded objectively based on renal weight, variation in size of tubule cell nuclei, and glomerular nuclear volume fraction. Irradiation was associated with loss of renal weight, increased variability of tubule nuclear size, and previously unappreciated changes in glomerular nuclear volume fraction. A classification index derived from a weighted combination of renal weight ratio and tubule cell nuclear variability correlates with radiation dose and with previously established subjective histologic grading of renal damage, and allows objective comparisons of various fractionation schedules.

Animals↗

Glutathione-dependent enzymes in intact rod outer segments.

We have compared the specific activities of glutathione-dependent enzymes in rod outer segments (ROS) and in whole retina of rabbits and rats, using three different assays. In the first, glutathione peroxidase (GSH-Px) activity was measured as the combined activities of the Se-dependent and Se-independent forms using cumene hydroxide as a substrate. In the second, Se-dependent GSH-Px alone was measured using hydrogen peroxide (H2O2) as a substrate. In the third, the combined activities of several enzymes, collectively known as GSH-S-transferase, were measured. The latter includes the activity of the Se-independent GSH-Px. GSH-Px activity (Se-dependent and Se-independent combined) in ROS of rat and rabbit were found to be 47.7 +/- 8.2 and 72.9 +/- 11.9 nmol of GSH oxidized min-1 mg-1 soluble protein, respectively. From whole retina, values were 67.3 +/- 6.0 and 128.8 +/- 12.3, respectively. Se-dependent GSH-Px specific activities from the above tissues were 43.5 +/- 2.9 (rat ROS). 70.6 +/- 11.3 (rabbit ROS), 30.6 +/- 9.6 (rat whole retina), and 113.2 +/- 12.2 (rabbit whole retina). GSH-S-transferase activity was negligible in rabbit ROS, whereas, in rat ROS, it was 40.4 +/- 8.0, expressed as nmol of S-2,4-dinitrophenylglutathione produced min-1 mg-1 soluble protein. In contrast, the GSH-S-transferase specific activity in whole rabbit retinas was about eight times that found in the rat retina (101.5 +/- 12.3 for rat retina and 885.3 +/- 60.0 for rabbit retina). These results demonstrate that ROS contain glutathione enzymes which are important in protecting membranes from oxidative stresses by reducing hydrogen peroxide and lipid hydroperoxides at the site of their formation.

Animals↗

A trial of superovulation in ovum donors undergoing uterine lavage.

In an attempt to increase the number of fertilized ova recoverable by uterine lavage, the authors superovulated ovum donors using a combination of clomiphene citrate and human menopausal gonadotropin. Six women underwent seven lavage cycles with uterine flushes performed 96, 120, 144, and 168 hours after ovulation and artificial insemination. Ova were recovered from three women between 96 and 144 hours after ovulation. However, no ova were recovered from the other three donors, two of whom were later noted to be pregnant. Retained pregnancies occurred despite postlavage administration of high-dose contraceptive pills, endometrial aspiration, and, in one case, RU 486. None of the infertile women became pregnant as a result of the trial. The authors conclude that, although superovulation may increase ovum production, without reliable contragestion, such practice is unsafe for ovum donors undergoing uterine lavage.

Adult↗

The effects of hyperventilation on cerebral blood flow in the rat with an open and closed carotid-jugular fistula.

Perturbations in cerebral hemodynamics at the time of ablation of an arteriovenous shunt have been regarded as important in the pathogenesis of swelling and hemorrhage complicating resection of arteriovenous malformations (AVMs). A carotid-jugular fistula model in the rat had previously been investigated and found to simulate in part the nonhemorrhagic pathophysiology of a large cerebral arteriovenous fistula. Utilizing this model and measuring cerebral blood flow in 14 regions with a [14C]iodoantipyrine autoradiographic technique, the effects of hypocapnea on the cerebral circulation in opened and closed fistulas were investigated. Regional cerebral blood flow (rCBF) in control animals ranged from a median of 53 to 64 ml/100 g/min at a partial arterial carbon dioxide pressure (PaCO2) of 28 +/- 2 mm Hg and 85 to 112 ml/100 g/min at a PaCO2 of 40 +/- 5 mm Hg. In animals with an open carotid-jugular fistula created 12 weeks before the study, these median rCBF values at comparable PaCO2 levels ranged, respectively, from 15 to 39 ml/100 g/min and 50 to 68 ml/100 g/min (the 25th percentile for the open fistula in the hypocapneic group was 15 ml/100 g/min in 5 of the 14 regions studied). In contrast, median rCBF in the closed fistula group ranged from 73 to 100 ml/100 g/min in hypocapneic animals and from 118 to 187 ml/100 g/min in normocapneic animals. These results demonstrate the preservation of CO2 reactivity; hypoperfusion in the presence of a carotid-jugular fistula, hyperemia on fistula occlusion, and the potential to induce cerebral ischemia with hyperventilation in this model of a cerebral arteriovenous fistula.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Improvement of cortical perfusion, intracellular pH, and electrocorticography by nimodipine during transient focal cerebral ischemia.

The alterations in metabolism and cerebral blood flow that occur following transient focal ischemia were studied in rabbits anesthetized with halothane and subjected to transient occlusion of an M2 segment of the middle cerebral artery (MCA). The parameters measured included intracellular brain pH and focal cortical blood flow (fCBF)--assessed by the umbelliferone technique--electrocorticograms, and cortical microcirculatory changes. A gradient of ischemia developed in the cortex between the patent and occluded vessels. Cortical sites with moderate and severely diminished flow were examined as a function of time before and after occlusion. Mean preocclusion fCBF was 50.8 +/- 2.1 ml/100 g/min, and brain pH was 6.99 +/- 0.04. Following occlusion, fCBF fell to 14.6 +/- 2.3 ml/100 g/min, with an intracellular pH of 6.53 +/- 0.03 in sites of severe ischemia in the territory of the occluded vessel. Sites between the patent and occluded branches revealed moderate changes in fCBF and intracellular pH of 26.7 +/- 3.6 ml/100 g/min and 6.74 +/- 0.03 ml/100 g/min, respectively. Sites adjacent to the patent M2 branch remained similar to baseline. Pretreatment intravenously with nimodipine, a dihydropyridine class of Ca2+ channel antagonist, improved flow in the territory of the occluded segment of the middle cerebral artery to 30.6 +/- 2.2 ml/100 g/min, while maintaining the brain pH at 6.83 +/- 0.03. Similarly, at sites intermediate between the patent and occluded M2 segments of the MCA, cortical blood flow remained at 53.5 +/- 4.0 ml/100 g/min, and the pH at 6.95 +/- 0.04, in 10 animals pretreated with nimodopine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗