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Biomedical subjects

E Brown

Publications and source records attributed to E Brown.

At least 199 records · Page 11Linked to original sources

How sensitive are immunometric assays for thyrotropin?

The usual method for calculation of the "sensitivity" of thyrotropin immunometric assays is multireplicate analysis of the zero analyte standard. Although this is a statistically valid estimate of the scatter likely to be found in the response variable, it is unrelated to normal analytical practice (usually analysis in duplicate) and estimates intra-assay errors only. This study was designed to assess the analytical performance of 10 immunometric assays used routinely for measurement of thyrotropin in human serum. Response data from each assay were accumulated to provide (a) an estimate of "sensitivity" from multireplicate analysis and (b) an estimate of "minimum detection limit," relating directly to errors associated with routine performance and derived from a minimum of 500 duplicate analyses. We conclude that the "minimum detection limit" should be promoted as a more meaningful measure of assay performance at low analyte concentrations than the "sensitivity" derived from multireplicate analysis of the zero-analyte standard.

Evaluation Studies as Topic↗

Distribution of synaptic inputs onto goldfish retinal ganglion cell dendrites.

Retinal ganglion cells in the goldfish were labeled by retrograde transport of horseradish peroxidase, and areas near the optic disk where the dendrites appeared to be completely filled were analyzed by electron microscopy. Only 6% of their inputs were ribbon synapses from bipolar cells; the other 94% of the inputs were conventional synapses mostly or entirely from amacrine cells. There were three strata of the inner plexiform layer with high densities of inputs to ganglion cells, the first centered at approx. 50% and the second at approx. 80% of the inner plexiform layer depth, as measured from the ganglion cell layer to the inner nuclear layer. These two strata comprised 25% of the volume but contained 41% of the inputs to ganglion cells. There were also two strata with very low densities of ganglion cell inputs located near the boundaries of the inner plexiform layer, from 0- to 15% and 90- to 100% of the depth. These strata, which also comprised 25% of the volume, contained only 7% of the inputs to retinal ganglion cells. These strata near the boundaries of the inner plexiform layer also contained 81% of the processes with large, dense-cored vesicles characteristic of peptidergic neurons. We concluded that each of the two sublaminae, a and b, identified previously by physiological criteria, could be further divided into at least two strata, one near the boundary of the inner plexiform layer with abundant peptidergic terminals and very few ganglion cell synapses and another near the center of the inner plexiform layer with numerous ganglion cell synapses. We also propose a hypothesis that could explain the functions of these additional strata.

Animals↗

Premature graduates of the newborn intensive care unit: a guide to followup.

Approximately 40,000 infants weighing less than 1500 grams are born in the United States each year. Caring for these infants after their discharge from the newborn intensive care unit is complex and difficult. The survival, growth, routine health care maintenance, neurologic and developmental outcome and assessment, and long-term medical complications are reviewed.

Cause of Death↗

Targeting the hospitalized elderly for geriatric consultation.

This empirical study reports the proportion of hospitalized elderly patients who were identified as frail. As a part of a randomized controlled trial, standardized criteria were developed to target the frail hospitalized elderly for geriatric consultation. Twelve-hundred patients aged 65 years and older admitted to the medical and surgical services at the Palo Alto Veterans Administration Medical Center were screened. Because of administrative exclusions of the randomized controlled trial (eg, short stay, lived too far away), 749 (62%) were excluded from the clinical screening process. The remaining 451 patients received clinical screening. Of these patients, almost two thirds (64%) were considered "too independent" to benefit from geriatric consultation (ie, independent in activities of daily living with short term illness), while 12% were judged "too impaired" to benefit (ie, had severe dementia or terminal cancer). Only 24% of those clinically screened (9% of the entire sample) were considered appropriate for geriatric consultation. Strikingly, over 42% of those patients aged 76 or older, were judged "too independent." These data suggest that a large majority of the hospitalized elderly may be too well to benefit from geriatric consultation, thus making targeting by age alone inefficient. A realistic estimate of the percentage of hospitalized patients appropriate for geriatric intervention lies somewhere between 18% (the combined percentage of those found appropriate and those already enrolled in geriatric programs) and 24% (the proportion of the clinically evaluated group found appropriate). Targeting of subjects may be accomplished inexpensively using the authors' explicit criteria. Such targeting may help focus the use of interdisciplinary geriatric expertise on those most in need.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗

Studies in the guinea-pig with ICI 185,282: a thromboxane A2 receptor antagonist.

The effects of ICI 185,282 (5(Z)-7-([ 2,4,5-cis]-4-O-hydroxyphenyl-2-trifluoromethyl-1, 3-dioxan-5-yl)heptenoic acid) have been studied on guinea-pig platelets and pulmonary smooth muscle in-vitro and in-vivo. When tested on guinea-pig lung parenchyma in-vitro. ICI 185,282 (1 x 10(-7) M) produced a significant shift in U-46619 response curves (concentration ratio of 13:3); the antagonist (1 x 10(-5) M) did not modify histamine responses. When tested on guinea-pig trachea in-vitro ICI 185,282 (1 x 10(-7) M) caused significant inhibition of U-46619 and PGD2 responses (concentration ratios of 8.3 and 14.1, respectively); the antagonist (1 x 10(-5) M proved less effective against contractions of PGF2 alpha, LTD4 and histamine (concentration ratios of 7.0, 1.5 and 1.6). When added to guinea-pig platelet rich plasma in-vitro, ICI 185,282 (x 10(-6), 1 x 10(-5) M) caused concentration-dependent parallel shifts to the right of U-46619 aggregation curves, yielding concentration ratios of 13.6 and 141.9, respectively. In-vitro, addition of ICI 185,282 (x 10(-5) M) to indomethacin-treated pulmonary smooth muscle did not modify resting tone, neither did it induce aggregation or swelling in platelet-rich plasma preparations. When administered orally to guinea-pigs ICI 185,282 (0.1, 0.5 mg kg-1) caused a significant inhibition of U-46619-induced platelet aggregation ex-vivo which persisted greater than or equal to 8 h. In-vivo, a single oral dose of ICI 185,282 (1 mg kg-1) inhibited bronchospasm induced by U-46619, PGD2, PGF2 alpha, arachidonic acid, LTD4 and PAF; responses to histamine were unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Analysis of antigenic determinants of retinal S-antigen with monoclonal antibodies.

Eight murine monoclonal antibodies to retinal S-antigen were found to recognize three antigenic clusters in competitive binding experiments. Variable patterns of immunohistochemical staining of retinal sections supported the competitive binding studies. Monoclonal antibodies to two of these three antigenic clusters on S-antigen reacted by Western immunoblotting with both intact S-antigen and two cyanogen bromide cleaved peptide fragments of bovine S-antigen. The binding of the monoclonal antibodies was localized to epitopes contained on two peptide fragments of 26,000 and 18,000 molecular weight. The same peptide fragments also react with polyclonal rat or rabbit antisera to bovine S-antigen. Monoclonal antibodies to the third antigenic cluster did not react with either intact or fragmented S-antigen in immunoblotting studies.

Animals↗

Hemorrhage, phenobarbital, and fluctuating cerebral blood flow velocity in the neonate.

Fifty-one sequential intubated babies with birth weights of less than 1,751 were evaluated by serial Doppler ultrasound during the first three days of life. These babies were part of a phenobarbital prophylaxis trial cohort study. Subependymal-intraventricular hemorrhage developed in 17 of the babies. Infants with subependymal-intraventricular hemorrhage, whether or not they received pancuronium or phenobarbital, had coefficients of variation comparable to those of babies without hemorrhage. Coefficient of variation values of the right were comparable to values obtained from the left anterior cerebral artery complex and did not appear to be consistently altered by the presence of subependymal-intraventricular hemorrhage. Coefficient of variation values appeared to be consistently greatest on day 1 and lowest on day 2. In addition, the values overall increased as the number of waves used to determine the coefficient of variation enlarged from five to 20. This phenomena, however, was not seen among pancuronium recipients and suggests that movement artifact may be a determinant of coefficient of variation values. We conclude that, when the best 20 waves are chosen to evaluate the coefficient of variation, no association exists between coefficient of variation values and development of subependymal-intraventricular hemorrhage or administration of phenobarbital.

Blood Flow Velocity↗

Thyroid and parathyroid surgery performed with patient under regional anesthesia.

Thyroid and parathyroid surgery is usually performed with the patient under general anesthesia; however, for selected patients regional anesthesia may be preferable. Between September 1977 and March 1986 regional anesthesia was used successfully as the sole anesthetic technique in 17 patients who underwent thyroid surgery and two patients who underwent parathyroid surgery. Procedures included two total thyroidectomies, 14 lobectomies or lobectomies with isthmusectomies, and one isthmusectomy. These 17 operations represent approximately 5% of the thyroid operations performed by the senior surgeon over the corresponding time. One patient underwent combined completion thyroidectomy and parathyroidectomy, and another patient underwent successful parathyroidectomy under regional anesthesia. In two additional patients, procedures could not be completed under regional anesthesia alone. In one of these two patients regional anesthesia appeared to effect a transient recurrent nerve paralysis. The indications for use of regional anesthesia have been primarily patient preference and associated cardiac or pulmonary disease. We now consider as contraindications to regional anesthesia patient apprehension about the technique, deafness, high spinal cord injury, recurrent laryngeal or phrenic nerve palsy, and allergy to local anesthesia. During this period, from 1977 to 1986, our administration of regional anesthesia has evolved from bilateral deep and superficial cervical plexus blocks to bilateral superficial blocks alone using bupivacaine with epinephrine, 1:200,000.

Adult↗

High extracellular Ca2+ and Mg2+ stimulate accumulation of inositol phosphates in bovine parathyroid cells.

We examined the effects of the divalent cations Ca2+ and Mg2+ on inositol phosphate accumulation in bovine parathyroid cells prelabelled with [3H]inositol to determine whether the high extracellular Ca2+ and Mg2+-evoked transients in cytosolic Ca2+ in these cells might result from increases in cellular IP3 levels. In the presence of Li+, both Ca2+ and Mg2+ produced rapid, 2-6-fold increases in IP3 and IP2 and a linear increase in IP of 6-8-fold at 30 min. Smaller (1.5-2-fold) increases in IP2 and IP3 were evident within 7.5-15 s upon exposure to high (3 mM) Ca2+ in the absence of Li+. The relative potencies of Ca2+ and Mg2+ (Ca2+ 3-fold more potent than Mg2+) in elevating inositol phosphates were similar to those for their effects in inhibiting PTH release. Fluoride (5 and 10 mM) also produced similar increases in inositol phosphate accumulation, presumably through activation of phospholipase C by a guanine nucleotide (G) protein-dependent process. Thus, high extracellular Ca2+ and Mg2+-induced spikes in cytosolic Ca2+ in bovine parathyroid cells may be mediated by increases in IP3, perhaps through a receptor-mediated process linked to phospholipase C by a G-protein.

Animals↗

Pulmonary aspergillosis in a horse with myelomonocytic leukemia.

Acute myelomonocytic leukemia was diagnosed in a 2-year-old Standardbred mare that had hind limb edema and fever unresponsive to antibiotics. The mare had anemia, thrombocytopenia, and leukocytosis, with circulating myeloblasts and monocytoid cells. A bone marrow specimen was hypercellular, with myeloblasts and monocytoid cells. Peroxidase, chloroacetate esterase, and alpha naphthyl acetate esterase activities were detected in many bone marrow cells. Interstitial pulmonary densities were seen radiographically. The mare was euthanatized and necropsied. Infiltrates of leukemic cells were found microscopically in specimens of spleen, lymph nodes, liver, kidneys, gastrointestinal tract, and lungs. Granulomas containing fungal hyphae were seen microscopically in the lungs, and Aspergillus sp was isolated from the lesions.

Animals↗

Efficacy of two insertions of 100-minute releasing quinacrine hydrochloride pellets for non-surgical female sterilization.

Extensive research has been undertaken to develop a simple method of non-surgical female sterilization. Zipper and associates identified quinacrine hydrochloride as a drug likely to produce tubal occlusion when placed into the uterus. Zipper's early work with a solution of quinacrine led to the development of quinacrine pellets, a delivery system that was designed to bring the quinacrine into prolonged contact with the tubal ostia through extended uterine retention. Three transcervical uterine insertions of 10-minute releasing quinacrine hydrochloride pellets performed at monthly intervals have produced a 12-month pregnancy rate of 3.3 per 100 women. The ultimate goal is to develop an effective, single insertion procedure, but the performance of the quinacrine pellets in occluding tubes has necessitated more than one insertion. FHI developed a 100-minute extended release pellet system with the expectation that more prolonged drug exposure would produce a higher rate of tubal closure. A study of the 100-minute releasing pellet system has been conducted in Santiago, Chile. Two monthly insertions in 112 women has resulted in a 12-month pregnancy rate of 2.0 per 100 women. Postprocedure problems occurring within the first year were reported by 13% of the women; most were minor and transitory.

Adult↗

The effects of stanozolol and boldenone undecylenate on plasma testosterone and gonadotropins and on testis histology in pony stallions.

Fifty 2- to 16- yr old pony stallions were randomly assigned to one of five treatments: Group 1, controls (no treatment); Group 2, 0.55 mg/kg stanozolol weekly for 13 treatments; Group 3, 1.1 mg/kg stanozolol every 3 wk for 5 treatments; Group 4, 1.1 mg/kg boldenone undecylenate every 3 wk for 5 treatments; and Group 5, 0.55 boldenone undecylenate weekly for 13 treatments. Mean plasma testosterone levels for Groups 2, 4, and 5 were elevated over controls (P<0.01) at 2, 8, and 9 wk, respectively. Testosterone levels for ponies in Group 3 did not differ from controls (P>0.05). There were no differences in mean plasma luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels among groups (P>0.05). Daily spermatid production per gram of testicular parenchyma (DSP/gm) in Group 5 was lower than in controls (P<0.05), whereas DSP/gm was not different among groups 1 to 4 (P>0.05). There were no differences among groups (P>0.05) in the percentage of Stage 8 tubules or relative number of Leydig cells. The mean diameter of Leydig cells was less for Group 5 than for controls (P<0.05), but was not different for Groups 1 to 3 (P>0.05).

Journal Article↗

Comparative biochemical analysis of purified S-antigen from human, bovine, porcine and rat retina.

Highly purified S-antigen from human, bovine, porcine and rat retina was used to ascertain the molecular weights, isoelectric points, amino-acid composition and presence of carbohydrate moieties. All S-antigen preparations comigrate to 50,000 MW on SDS-polyacrylamide gels and demonstrate microheterogeneity upon isoelectric focusing. Human S-antigen exhibits two bands at pH 5.9 and 5.6, whilst with bovine S-antigen a broad band at pH 5.9 was observed. Porcine and rat S-antigen gave four bands, focusing between pH 5.0-5.6. Two-dimensional gel analysis revealed that all the four focused porcine polypeptides migrate to 50,000 MW. Western-blot analysis following isoelectric focusing of human and porcine S-antigen showed that all polypeptide bands react specifically with polyclonal and monoclonal antibodies to S-antigen. The reasons for the apparent heterogeneity of S-antigen by isoelectric focusing are discussed. All S-antigen preparations were weakly positive for periodic acid Schiff staining, and specifically bound radiolabelled Lens culinaris lectin on Western-blot analysis. These results confirm the glycoprotein nature of S-antigen which may explain the finding of multiple bands found on isoelectric focusing. Amino-acid analysis reveals the high percentage of non-polar amino acids and may explain the apparent hydrophobic behaviour of the isolated protein.

Amino Acids↗

Increase in life expectancy for mice fed diethylhydroxylamine (DEHA).

ICR Swiss strain mice were fed diethylhydroxylamine (DEHA) for life starting at 44 days of age at 10, 30, 100, and 300 mg/kg-day. The 10 and 30 mg/kg-day males and the 10 mg/kg-day females showed an increase in mean age of death of 76 (12.7%), 45 (7.5%), and 51 (7.4%) days, respectively, compared to controls. The respective confidence levels are 99.2, 90.0, and 92.9% that these results are significant by Student's t test.

Animals↗