The evolving purposes of the autopsy: twenty-first-century values from an eighteenth-century procedure.
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Biomedical subjects
Publications and source records attributed to R E Anderson.
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We performed a pharmacodynamic comparison of human urinary follicle-stimulating hormone (hFSH) and human menopausal gonadotropin (hMG) to characterize differences in the bioavailability of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as to compare estrogen responses in normal women and those with polycystic ovary syndrome (PCOS). Ten women with PCOS and ten normal ovulatory controls were randomized to receive a single dose (2 ampules) of either hFSH or hMG. Serum LH decreased significantly following hFSH with responses occurring earlier in controls (24.5 +/- 10.9% after 30 minutes) than in PCOS patients (27.3 +/- 7.5% after 18 hours). After hMG, LH increased only in controls (33.8 +/- 16.3%). An FSH increment following hFSH was observed in both PCOS patients (54.7 +/- 24.8%) and controls (74.6 +/- 36.8%), with peak responses at 6 and 4 hours, respectively. However, after hMG, FSH increased only in controls. The LH/FSH ratio after hFSH decreased, with the nadir at 18 hours (1.438 +/- 0.183) being similar to baseline LH/FSH ratios of controls (1.433 +/- 0.341). Serum estradiol (E2) increased following hMG, with peak responses after 18 hours, in both PCOS patients (75.4 +/- 28.6%) and controls (88.5 +/- 32.5%). The peak E2 response to hFSH was observed to be earlier in PCOS patients (147 +/- 34%), occurring after 12 hours, compared with controls (58 +/- 29% after 18 hours).
It is possible that a genetic defect observed in the prcd poodle involves the abnormality of an enzyme which functions in phospholipid or lipoprotein metabolism. In our studies thus far, we have been unable to detect any defect in retinal phospholipid biosynthesis, but we have noted a decrease in plasma levels of 22:6w3 which may be a result of an enzyme defect in liver biosynthesis of 22:6w3 from its dietary precursor, linolenic acid, or some defect in the blood lipoprotein transport of this essential fatty acid. If 22:6w3 is essential to the normal elaboration and functioning of the photoreceptor outer segment, it is possible that decreased access to this fatty acid due to lower blood levels of 22:6w3 could cause photoreceptor abnormalities. Further studies are needed to confirm the possible defect in delta-4 desaturase activity and possible dietary modification of the course of this prcd retinal degeneration.
An evaluation of 629 pathologists engaged in community hospital and private laboratory practice and representing 601 pathology practices of varying size shows surprising uniformity in the distribution of professional effort. On average, pathologists in community practice distribute their effort as follows: surgical pathology, 34.6%; autopsy pathology, 6.7%; cytology, 8.8%; clinical pathology, 18.0%; teaching, 6.0%; research and development, 2.3%; laboratory administration, 17.5%; hospital administration, 2.9%; and other, 3.2%. The average community pathologist is male, 52 years of age, and a graduate of an American medical school (60%). When surveyed in 1986, community pathologists worked an average of 50 hours per week and retired at an average age of 62 years.
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We have presented an unusual case of CJD in which the magnetic resonance images obtained four months before death revealed high signal intensity in the caudate nuclei bilaterally. These findings correspond to severe involvement of this region at autopsy. This radiologic pattern has not generally been included in the differential diagnosis of CJD.
CD4 and CD8 T lymphocytes of three groups of men infected by the human immunodeficiency virus (HIV) were examined twice yearly for 36 months to elucidate the temporal trends in T lymphocytes during infection. The three groups were 37 HIV seroconverters, 304 prevalent HIV seropositives remaining free of the acquired immunodeficiency syndrome (AIDS), and 69 men who developed AIDS during observation. Six months before seroconversion, CD4 levels were similar among HIV seroconverters and 356 seronegative controls. Within 18 months of seroconversion, mean CD4 levels fell to the level of the prevalent seropositives at study entry. From there, the rate of decline slowed. CD8 lymphocyte counts rose dramatically at seroconversion. Among AIDS-free prevalent seropositives, CD4 levels fell steadily over 36 months of observation. By contrast, CD8 cell levels rose slowly. Among men who developed AIDS, mean CD4 levels fell more rapidly again during the 18 months prior to diagnosis. CD8 cell levels remained elevated until 6-12 months before diagnosis, when they began to fall.
A method for the quantitative analysis of molecular species of 1,2-diacylglycerol acetates (1,2-DGAC) containing polyunsaturated fatty acids is described. Phosphatidylethanolamine (PE) isolated from frog retina was used to test the method. PE was converted to 1,2-DGAC by acetolysis. The molecular species of the 1,2-DGAC were resolved by reverse-phase high performance liquid chromatography (HPLC), detected by UV absorption spectroscopy at 210 nm, and identified by gas-liquid chromatography (GLC) of the fatty acid methyl esters (FAME). Molar response curves were generated for each DGAC molecular species that eluted as a single entity from HPLC by determining the moles of fatty acids in the molecular species collected and the response (peak area unit) of the UV detector. Each molecular species response curve was linear from about 10 pmoles to 4-8 nmoles, allowing the slope of each curve to be used as a molar absorptivity. This method provides a means for quantification of most of the molecular species of all glycerolipid classes.
As viewed by pathology chairmen, the primary reasons for the decline in interest in the autopsy are: (1) a feeling among physicians that everything is known about the case; (2) poor education of medical students and clinical house staff concerning the importance of the autopsy, which carries over to the practitioner; and (3) lack of interest on the part of pathologists. Negative attitudes on the part of clinicians were seen as the primary factor that serves to inhibit enthusiasm for the autopsy on the part of pathology house staff. Lack of prompt and appropriate communication with the attending physician and uneven quality of prosectors are seen as major inhibitors to successful autopsy services. Chairmen of departments of pathology support an approximate doubling of the autopsy rate in their institutions (from 30% to 64%), although 42.5% of chairmen had not discussed their wishes concerning autopsy with the next of kin and only 42% regularly attend gross conference. These perceptions are remarkably similar to those provided by chairmen of departments of medicine and surgery as a part of a previous survey. On the basis of these inputs, several recommendations designed to improve the local emphasis on the autopsy service are provided.
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We have studied the de novo synthesis and subsequent turnover of major docosahexaenoate-containing molecular species in frog rod outer segment (ROS) phospholipids following intravitreal injection of [2-3H]glycerol. On selected days after injection, ROS were prepared and phospholipids extracted. Phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS) were isolated and converted to diradylglycerols with phospholipase C. Diradylglycerols were derivatized with benzoic anhydride and resolved into diacylglycerobenzoates and ether-linked glycerobenzoates. The diacylglycerobenzoates were fractionated into molecular species by HPLC, quantitated, and counted for radioactivity. Label was incorporated into ROS phospholipids by day 1 and was followed up through the eighth day. The dipolyenoic species 22:6-22:6 from PC showed a 3-5 times higher radiospecific activity than the same species from either PE or PS. In PC, the specific activities of 16:0-22:6 and 18:0-22:6 were 3-5 times lower than the specific activity of 22:6-22:6. In contrast, for PE, the specific activities of 16:0-22:6 and 18:0-22:6 were 2-5 times higher than that of 22:6-22:6. The specific activities of 18:0-22:6 and 22:6-22:6 were similar in PS. Specific activities of the docosahexaenoate-containing species began approximating an exponential decline 6-8 days postinjection and continued through the 31st day. The rate of decline was determined by calculating the half-life of each molecular species, which was used as a measure of the turnover of the species. The species 22:6-22:6-PE and 18:0-22:6-PE showed a 2-3 times slower turnover rate than the corresponding species from either PC or PS.(ABSTRACT TRUNCATED AT 250 WORDS)
The metabolism of myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] consists of two pathways: dephosphorylation by 5-phosphomonoesterase(s) produces inositol 1,4-bisphosphate, and phosphorylation by Ins(1,4,5)P3 3-kinase yields inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4]. The requirements for Ins(1,4,5)P3 kinase activity in retina were characterized. Apparent Km values for ATP and Ins(1,4,5)P3 are 1.4 mM and 1.3 microM respectively. A direct demonstration of phosphorylation of Ins(1,4,5)P3 by [gamma-32P]ATP was achieved. Characterization of the 32P-labelled product revealed that it had the expected chromatographic and electrophoretic properties of Ins(1,3,4,5)P4.
We investigated the ability of a single, random, urinary pregnanediol-3 alpha-glucuronide level to differentiate early intrauterine from ectopic pregnancy. Thirty-four patients with intrauterine gestations were compared with 60 patients with ectopic pregnancies. Urinary pregnanediol-3 alpha-glucuronide was measured by radioimmunoassay and enzyme immunoassay. Compared with intrauterine gestations, results demonstrate that urinary pregnanediol-3 alpha-glucuronide is significantly depressed in ectopic pregnancies: 24.5 +/- 2.2 versus 4.8 +/- 0.7 micrograms/ml (p = 0.0001). Urinary pregnanediol-3 alpha-glucuronide levels obtained by conventional radioimmunoassay correlated closely with values measured in minutes with enzyme immunoassay (r = 0.95, p = 0.0001), and with serum progesterone (r = 0.74, p = 0.0001). Urinary pregnanediol-3 alpha-glucuronide measured by enzyme immunoassay exhibited predictive values for detecting ectopic gestations comparable with random serum progesterone or serum beta-human chorionic gonadotropin values. We conclude that ectopic gestations demonstrate a reduced level of urinary pregnanediol-3 alpha-glucuronide (55/60 cases) detectable with a rapid enzyme immunoassay, which makes this assay a practical screening test in early pregnancy.
Experiments were conducted to examine the possible interaction between retinal taurine depletion and environmental lighting in causing photoreceptor cell degeneration. Albino rats were raised from birth in either dim (2 lx) or relatively bright (300 lx) cyclic light. Beginning at weaning, half the animals from both light environments were taurine-depleted by treating them for 10 weeks with guanidinoethyl sulfonate as a 1% solution in their drinking water. The remaining animals were given ordinary tap-water and served as controls. In the 2 lx light environment, taurine depletion caused a decrease in electroretinogram (ERG) a- and b-wave amplitude of 36 and 46%, respectively; however, no photoreceptor cells were lost in this group. Tap-water controls kept in the 300 lx light environment had a 59- and 43% decrease in ERG a- and b-wave amplitude, respectively, and a 21% reduction in the number of photoreceptor cells. In contrast to the other groups, animals that were taurine-depleted in the 300 lx environment showed a marked retinal degeneration. ERG a- and b-wave amplitude was decreased by 94- and 89% respectively and there was a 62% loss of photoreceptor cells. The greatest cell loss occurred in the central superior region of the retina, in which the outer nuclear layer was typically reduced to one to two rows of nuclei. The results of a two-way analysis of variance applied to the data indicated that the effects of taurine depletion on the retina were greater in the 300 lx as compared with the 2 lx environment in terms of loss of photoreceptor cells and reduction in log ERG a- and b-wave amplitude. These findings demonstrate a synergism between environmental lighting and taurine depletion in causing photoreceptor cell degeneration.
The photoreceptor, like many other cells, undergoes receptor-mediated breakdown of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2]. The lack of phosphatidylinositol (PdtIns) breakdown during receptor stimulation suggests the existence of a phospholipase C specific for polyphosphoinositides. Phospholipase C activity in frog rod outer segments was assayed with several substrates. The activity was selective for the polyphosphoinositides, phosphatidylinositol 4-phosphate [PtdIns(4)P] and PtdIns(4,5)P2. PtdIns was hydrolysed at 2% of the rate of hydrolysis of PtdIns(4,5)P2. No activity was detected when phosphatidylcholine, phosphatidylserine, or phosphatidylethanolamine were used as substrates. The enzymatic activity was optimal at neutral pH. These findings suggest, but do not prove, that this activity might contain the light-regulated phospholipase C of the photoreceptor.
To further investigate prolactin (PRL) secretion in polycystic ovary syndrome (PCO), the authors evaluated immunoreactive (immuno) and bioactive (bio) PRL levels in the basal state and in response to provocative testing with intravenous dopamine (DA), metoclopramide (MCP), and gonadotropin-releasing hormone (GnRH), before and after disulfiram. Basal measurements of immuno-PRL, bio-PRL, and the ratio of bio/immuno-PRL were similar in PCO and controls. The immuno-PRL decrement after DA was greater than that of bio-PRL in both groups (P less than 0.05). After MCP, immuno-PRL increased more than bio-PRL in PCO (P less than 0.01), and this immuno-PRL increment was greater than that of controls (P less than 0.05). Bio-PRL and immuno-PRL increased after GnRH in PCO, but not controls, and these responses were inhibited by disulfiram. These data confirm PRL hypersecretion in some women with PCO, which is better expressed by immunoreactivity than bioactivity. Given the assay systems and patients studied, bioactivity
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