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Biomedical subjects

J C Roberts

Publications and source records attributed to J C Roberts.

At least 37 records · Page 2Linked to original sources
PubMed1998

Comparison of in vitro activity of trovafloxacin against gram-positive and gram-negative organisms with quinolones and beta-lactam antimicrobial agents.

The in vitro activity of trovafloxacin against 721 Gram-negative and 498 Gram-positive organisms was determined by the standard microdilution broth method using commercially prepared frozen microtiter plates. The activity of trovafloxacin was compared to ofloxacin, ciprofloxacin, amoxicillin/clavulanate, ampicillin/sulbactam (1:1), piperacillin/tazobactam, ceftriaxone, and imipenem. Trovafloxacin had equal or greater activity compared with the other agents tested against Citrobacter diversus, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Stenotrophomonas maltophilia, Serratia marcescens, staphylococci, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, group G streptococci, Enterococcus faecalis, and E. faecium. The reliability of the commercially prepared plates for testing the in vitro activity of the quinolones was evaluated by comparing identical isolates also tested by broth microdilution using laboratory prepared plates. The commercially prepared plates generally correlated, within one- to twofold dilutions, with the laboratory prepared plates. There was, however, a large discrepancy obtained when testing Enterobacter agglomerans and E. cloacae, where the commercially prepared plates yielded a significantly higher MIC90 value.

4-Quinolones↗
PubMed1998

Differential chemoprotection against acetaminophen-induced hepatotoxicity by latentiated L-cysteines.

Novel thiazolidine prodrugs were prepared by the condensation of L-cysteine with aldose disaccharides. Using a disaccharide in prodrug construction allows for a terminal cyclic sugar moiety to be present on the prodrug, which may allow the delivery of the agent to specific receptors, such as the asialoglycoprotein receptor (ASGPR) of hepatocytes, that require specific structural motifs for recognition. Three L-cysteine prodrugs were synthesized with a pendant cyclic galactose moiety; two related glucose-bearing prodrugs were synthesized for comparison. The prodrugs were designed to release L-cysteine, which is then available to support glutathione (GSH) biosynthesis and provide cytoprotection against a variety of toxic insults. Protection studies in Swiss-Webster mice used acetaminophen (575 mg/kg), a well-documented hepatotoxin which depletes GSH at overdose. Three prodrugs performed exceptionally well against acetaminophen-induced hepatotoxicity, as measured by increased survival and improved histological profiles of liver tissue after 48 h. In further experimentation, two of the disaccharide-based prodrugs, prepared from alpha- and beta-lactose, were compared with the monosaccharide-based compound prepared from ribose. Co-administration of the selected prodrugs with a 400 mg/kg dose of acetaminophen to Swiss-Webster mice prevented the short-term depletion in hepatic GSH and also reduced hepatotoxicity as determined by histological damage and serum levels of alanine aminotransferase. A single dose of the prodrugs alone had no effect on hepatic drug metabolizing enzymes [glutathione S-transferase (GST), NAD(P)H:quinone oxidoreductase (QOR), UDP-glucuronosyltransferase (UGT), and cytochrome P450], but, concordant with the reduction of hepatotoxicity, the latentiated forms prevented the significant elevation in QOR activity and mRNA and GST mRNA elicited by acetaminophen itself. GST activity, UGT activity and mRNA, and cytochrome P450 concentration were all unaffected by acetaminophen or the prodrugs. These studies identified novel L-cysteine prodrugs with potentially useful hepatoprotective activity. However, no structure-activity relationships were obvious. In addition, the occurrence of targeted delivery to hepatocytes remains ambiguous.

Acetaminophen↗
PubMed1997

Glass peek composite promotes proliferation and osteocalcin production of human osteoblastic cells.

An isoelastic intramedullary implant has been developed using a composite of polyetheretherketone and 10% random, chopped E-glass fibers (GPEEK). The effect of this novel material on human bone cells has not been defined. The objective of this study was to test whether GPEEK supported the proliferation of the human bone cell line MG63, which exhibits osteoblastlike characteristics. Cells (1 x 10(5)/mL) were propagated on GPEEK discs with three different surface roughnesses (3, 6, and 9 microns) and on polystyrene plates, for comparison. The reaction of MG63 osteoblastlike cells to the GPEEK polymer composite was analyzed by determination of cell yield, osteocalcin production, and levels of alkaline phosphatase. The viable cells that were retrieved from the GPEEK discs of all three surface roughness had an approximate sixfold increase in number. Osteoblastic function of the cells, indicated by osteocalcin production, was unimpaired after a 5-day culture on the three surfaces of GPEEK. The highest level of osteocalcin was produced by osteoblastic cells propagated on GPEEK with a 9 microns surface roughness. The levels of alkaline phosphatase of these cells were similarly greater for the different degrees of surface roughness. Overall, this study demonstrates that GPEEK supported proliferation of osteoblastlike cells and provided a favorable environment for the continued production of osteocalcin in vitro.

Benzophenones↗
PubMed1997

Radiation protection by alpha-methyl-homocysteine thiolactone in vitro.

The radiation protective effect of thiol compounds is unequivocal and their use is only limited by their toxic effects. We used the principle of alpha alkylation, which renders amino acids unmetabolizable, to reduce the toxicity of homocysteine. This product, alpha-methyl-homocysteine thio-lactone, was tested for toxicity and radiation protective effect along with known protectors L-cysteine, cysteamine and WR 1065 in cell culture using V79-4 Chinese hamster lung cells. The three-day growth curve assays, useful to measure overall effects on cell growth, revealed lowest toxicity for alpha-methyl-homocysteine thiolactone (GL-2). Clonogenic survival tests, used to evaluate the retention of reproductive integrity, were carried out and revealed that GL-2 had no adverse effects in this test system. Radiation protection tests showed that GL-2 exhibited protective activity against radiation induced lethality above that seen with cysteine and cysteamine, but below WR 1065. However, GL-2 showed little or no negative effects toward the cell itself, in direct contrast to WR 1065. Our findings show a potentially important tool and principle to reduce toxicity of radiation protectors with analogous structures.

Animals↗
PubMed1997

Preparation and biodistribution of copper-67-labeled porphyrins and porphyrin-A6H immunoconjugates.

The synthetic porphyrins, N-benzyl-5,10,15,20-tetrakis (4-carboxyphenyl) porphine (N-bzHTCPP) and N-4-nitrobenzyl-5-(4-carboxyphenyl)-10,15,20-tris(4-sulfophenyl) porphine (N-bzHCS3P), represent excellent radiocopper chelating agents that may find utility in antibody-mediated diagnosis and/or therapy. N-bzHCS3P was conjugated to an anti-renal cell carcinoma (RCC) antibody, A6H, and labeled with copper-67. 67CuCS3P-A6H was studied for its biodistribution in human RCC xenograft-bearing nude mice, along with the radiolabeled free porphyrins. The porphyrins resulted in tumor:blood ratios in the range of 3 to 4 after 48 h. The radiolabeled antibody achieved a tumor:blood ratio of over 16 after 45 h, indicating accumulation at the desired site. However, unwanted localization also occurred in the liver and spleen, which will have to be rectified before realizing the full potential of this approach.

Animals↗
PubMed1997

Characterization of NK3 receptors in rabbit isolated iris sphincter muscle.

1. Tachykinin NK3 receptors were characterized in the rabbit isolated iris sphincter muscle by use of autoradiography and in vitro functional studies. 2. [125I]-[MePhe7]-neurokinin B (NKB) (1nM), a selective NK3 receptor agonist, specifically labelled a population of NK3 receptors that were uniformly distributed throughout the rabbit iris sphincter muscle. This labelling was inhibited by unlabelled [MePhe7]-NKB (1 microM) but not by the NK1 receptor antagonist CP 99994 (1 microM). 3. In the presence of CP 99994 (1 microM), the selective NK3 receptor agonists senktide (n = 14) and [Pro7]-NKB (n = 4), and the natural preferred ligand for the NK3 receptor, NKB (n = 8), were potent contractile agents in the rabbit iris sphincter muscle. They all produced monophasic concentration-effect curves with pD2 values of 9.53 +/- 0.08, 8.56 +/- 0.09 and 9.75 +/- 0.09, and nH values of 0.93 +/- 0.03, 1.53 +/- 0.17 and 0.76 +/- 0.06, respectively. [MePhe7]-NKB (n = 12) was also a potent agonist, but produced shallow concentration-effect curves which appeared biphasic (nH = 0.45 +/- 0.04). 4. Contractile responses to senktide were surmountably antagonized in a concentration-dependent manner by the selective non-peptide NK3 receptor antagonist, SR 142801 (3-30 nM; pA2 = 8.9; slope = 0.99) and the non-peptide NK2/NK3 receptor antagonist, SR 48968 (3-30 microM; pA2 = 6.1; slope = 1.5). These pA2 values were consistent with functional rabbit NK3 receptors more closely resembling guinea-pig and human NK3 receptors, than rat NK3 receptors. SR 142801 (10-100 nM) and SR 48968 (3 and 30 microM) inhibited responses to low (< or = 1 nM) but not higher (> 1 nM) concentrations of [MePhe7]-NKB, and concentration-effect curves to [MePhe7]-NKb became steeper and monophasic in the presence of either antagonist. 5. SR 142801 (3-30 nM) and SR 48968 (3-30 microM) also surmountably antagonized concentration-effect curves to [Pro7]-NKB and NKB, although results were more difficult to interpret, since the relationship between log concentration-ratios and the concentration of antagonist used did not adhere to the Schild equation. However, analysis of data with the lowest concentration of SR 142801 (3 nM) tested against NKB, and SR 48968 (3 microM) tested against [Pro7]-NKB and NKB, yielded apparent pA2 estimates of 9.3, 6.8 and 6.4, respectively, consistent with blockade of NK3 receptors. 6. SR 142801 (100 nM) had no effect on contractions induced by transmural nerve stimulation (2 Hz, 0.3 ms, 20 V for 30 s), whereas CP 99994 (1 microM) abolished these responses. 7. Phenoxybenzamine pretreatment (20 microM, 10 min) markedly reduced maximum responses to [MePhe7]-NKB (from 101 +/- 6.2% to 38 +/- 9.5% reference contraction, n = 4) and induced a marked (10 fold) rightward shift in the concentration-effect curve. The residual responses to [MePhe7]-NKB after phenoxybenzamine pretreatment were unaffected by 1 microM CP 99994 (maximum response = 41 +/- 9.4%, n = 4). 8. These results demonstrate autoradiographically and functionally, the presence of NK3 receptors in rabbit iris sphincter muscle that mediate contractile responses to NK3 receptor agonists, but not to sensory trigeminal nerve simulation. The present data with senktide and selective NK3 receptor antagonists suggest that functional rabbit NK3 receptors more closely resemble human and guinea-pig NK3 receptors than rat NK3 receptors. However, the pharmacological profiles of [MePhe7]-NKB, SR 142801 and SR 48968 suggest the presence of an 'atypical' NK3 receptor or a heterogeneous population of NK3 receptors in this tissue.

Adrenergic alpha-Antagonists↗
PubMed1997

Modulation of radiation-induced apoptosis by thiolamines.

Exposure to the thiolamine radioprotector N-(2-mercaptoethyl)-1,3-propanediamine (WR-1065) induced apoptosis in the mouse TB8.3 hybridoma after a 60-min (LD50 = 4.5 mM) or during a 20-h (LD50 = 0.15 mM) exposure. In contrast, a 20-h exposure to 17 mM L-cysteine or 10 mM cysteamine was required to induce 50% apoptosis within 20 h. Apoptosis was not induced by either a 60-min or 20-h exposure to 10 mM of the thiazolidine prodrugs ribose-cysteine (RibCys) or ribose-cysteamine (RibCyst). Thiolamine-induced apoptosis appeared to be a p53-independent process since it was induced by WR-1065 exposure in human HL60 cells. Exposure to WR-1065 (4 mM for 15 min) or cysteine (10 mM for 60 min) before and during irradiation protected cells against the induction of both DNA double-strand breaks and apoptosis, while exposure to RibCys (10 mM for 3 h) did not. Treatment with either WR-1065, cysteine, RibCys or RibCyst for 60 min beginning 60 min after irradiation did not affect the level of radiation-induced apoptosis. In contrast, treatment with either cysteine, cysteamine or RibCys for 20 h beginning 60 min after irradiation enhanced radiation-induced apoptosis. Similar experiments could not be conducted with WR-1065 because of its extreme toxicity. Our results indicate that thiolamine enhancement of radiation-induced apoptosis is not involved in their previously reported capacity to reduce radiation-induced mutations.

Animals↗
PubMed1997

The effects of SB 206284A, a novel neuronal calcium-channel antagonist, in models of cerebral ischemia.

The effects of SB 206284A, 1-[7-(4-benzyloxyphenoxy)heptyl] piperidine hydrochloride, have been investigated in vitro on calcium and sodium currents in rat-cultured dorsal root ganglion (DRG) neurones and potassium-mediated calcium influx in rat synaptosomes. Cardiovascular hemodynamic effects in both anesthetized and conscious rats, and neuroprotective activity in in vivo cerebral ischemia models were also investigated. In the rat DRG cells, SB 206284A caused almost complete block of the sustained inward Ca2+ current (IC50 = 2.4 microM), suggesting that the compound is an effective blocker of slowly inactivating, high-voltage calcium current. SB 206284A reduced locomotor hyperactivity in the gerbil bilateral carotid artery occlusion model without affecting ischemia-induced damage in the hippocampal CA1 region. In the rat middle cerebral artery occlusion model, SB 206284A reduced lesion volume in the posterior forebrain, and in the rat photochemical cortical lesion model, lesion volume was reduced even when treatment was delayed until 4 hours after occlusion. At neuroprotective doses, SB 206284A had no cardiovascular effects. These findings show that SB 206284A is a novel calcium channel antagonist that shows neuroprotective properties.

Animals↗
PubMed1997

Chromaffin cell epinephrine secretion mediated by a macrophage peptide: the role of endotoxin.

Recent studies show that mononuclear cells release a small peptide (molecular weight < 3,000) that stimulates chromaffin cell epinephrine secretion (1). The present study demonstrates that endotoxin (ETX) enhances this mononuclear cell-mediated epinephrine secretion and examines the potential mechanism for regulation of this peptide. Mononuclear cells from bovine spleen were cultured 24 h in serum-free media after which the supernatant (conditioned media, CM) was harvested and filtered to remove molecules with a molecular weight greater than 3,000. In vitro epinephrine secretion from bovine chromaffin cells was used as a test system and CM-secretion expressed as a percentage of total cell content. ETX challenge (1 microgram/mL) of mononuclear cell cultures significantly enhanced bioactivity of CM (control-CM = 11.8 +/- .7, ETX-CM = 17.7 +/- 2.8). Separation of cell populations by adherence to plastic revealed that T cell and/or B cell populations were the main source of the bioactive peptide(s) in unstimulated cell cultures (T/B cell = 12.9 +/- .7, M phi = 6.2 +/- .8). In contrast, ETX induced significant bioactive peptide release from the macrophage population (M phi = 6.2 +/- .8, ETX-M phi = 15.9 +/- 2.8). Polyacrylamide gel analysis revealed a small peptide in nonadherent cell CM that was present only in ETX-challenged macrophage cultures. Additionally, data are presented that demonstrate a correlation between CM bioactivity and protease activity in CM. Proteases secreted from mononuclear cells in response to ETX is hypothesized to cleave the bioactive peptide from a larger "parent" protein. This peptide may play a role in the elevation of plasma catecholamines observed in the setting of critical injury and illness and contribute to development of the systemic inflammatory response syndrome (SIRS) and subsequent shock states.

Animals↗
PubMed1996

Preliminary biological evaluation of polyamidoamine (PAMAM) Starburst dendrimers.

PAMAM Starburst dendrimers are spherical macromolecules composed of repeating polyamidoamino units. They can be produced in successive "generations," each with a defined size, molecular weight, and number of terminal amino groups. Because of these well-defined characteristics, PAMAMs are finding utility in a variety of applications, many of which are biological in nature. Little is known, however, about the biological behavior of the PAMAMs, which is critical to their use in vivo. Generation 3 (G3; MW = 5,147; 24 terminal amines), 5 (G5; MW = 21,563; 96 amines), and 7 (G7; MW = 87,227; 384 amines) PAMAMs were studied in V79 cells or in Swiss-Webster, mice for a number of biological properties, including (1) in vitro toxicity, (2) in vivo toxicity, (3) immunogenicity, and (4) biodistribution. Potential biological complications were observed only with G7 at the highest level tested. No evidence of immunogenicity was seen. The biodistribution properties of the Starburst dendrimers were rather unusual. G3 showed the highest accumulation in kidney tissue (approximately 15% ID/g over 48 h); G5 and G7 appeared to preferentially localize in the pancreas (peak levels approximately 32% ID/g at 24 h, and approximately 20% ID/g at 2 h, respectively). In addition, G7 showed extremely high urinary excretion, with values of 46 and 74% ID/g at 2 and 4 h, respectively. In general, the dendrimers did not exhibit properties that would preclude their use in biological applications. Depending on the situation (desired endpoint, dose, and generation used), however, the biodistribution of biological preparations should be carefully studied.

Animals↗
PubMed1996

Motor dysfunction in a photothrombotic focal ischaemia model.

The study of behavioural deficits resulting from cerebral infarction in animal models of stroke has in the past taken second place to histological assessment. This is particularly true of the photothrombotic lesion model. Most tests currently used to measure motor deficits use a scoring system to quantify parameters such as beam walking. The present study set out to characterise a simple and objective assessment for motor impairment in the photothrombotic cortical lesion model. Rats were assessed on a number of motor function tests, i.e. gross locomotor activity, rotarod, and grip strength. After the establishment of stable baselines, cortical photothrombotic lesions were induced, after which the animals were re-tested for a further 18 days. The presence of cortical photothrombotic lesions significantly imparied the rats' performance on the rotarod and grip-strength tests. The deficit observed with the grip-strength task appeared 24 h postsurgery, but was much reduced by day 18 postsurgery. The rotarod test revealed an effect that took longer to establish, but which was more persistent. Gross locomotor activity was not affected. These data suggest that bilateral photothrombotic lesions of the prefrontal cortex produce deficits that can be detected by rotarod and grip-strength tasks.

Animals↗
PubMed1995

Efficacy of radioprotective agents in preventing small and large bowel radiation injury.

PURPOSE: A variety of adjuvant treatments and cytoprotective agents have been proposed to lessen the toxicity of radiation therapy. The following study was designed to evaluate the benefit of six agents or combinations using anastomotic bursting strength as a measure of transmural radiation injury. METHODS: The 40-Gy study consisted of the following. Seventy-two male Sprague-Dawley rats were divided into eight equal groups: nonradiated control, radiated untreated control, and six radiated treated groups. The radioprotective treatments included ribose-cysteine (Rib-Cys), WR-2721, glutamine, vitamin E, MgCl2/adenosine triphosphate, and RibCys/glutamine in combination. Radiated animals received 40 Gy to the abdomen. Two weeks after radiation, all animals underwent small bowel and colonic resection with primary anastomosis. Animals were sacrificed one week postoperatively, at which time anastomoses were evaluated and bursting strengths determined. The 70-Gy study consisted of the following. The same protocol was repeated for five groups of nine rats divided into nonradiated, radiated untreated, and three radiated treated groups receiving RibCys (8 mmol/kg), RibCys (20 mmol/kg), and WR-2721. All radiated animals received 70-Gy doses. RESULTS: In the 40-Gy group, there were 10 radiation-related deaths and 6 anastomotic leaks among 70 rats studied. None of the differences between groups were significant. Nonradiated control group small bowel and large bowel anastomotic bursting pressures were significantly elevated compared with all radiated groups. Compared with radiated controls, there were significant improvements in small bowel bursting strength in the RibCys, WR-2721, RibCys-glutamine, and vitamin E groups and significant improvement in colonic bursting strength in MgCl2/adenosine triphosphate, WR-2721, and RibCys groups. In the 70-Gy group, all nine nonradiated control rats survived. All eight untreated radiated control rats died, four of eight WR-2721 animals died (P = 0.03), all RibCys (8 mmol/kg) animals died (P = 0.03), and three of nine treated with RibCys (20 mmol/kg) survived (P = 0.08). CONCLUSIONS: WR-2721 and RibCys gave consistent protection against large and small bowel radiation injury. The lower incidence of treatment-related toxicity and potentially equal or greater radioprotective effects may make RibCys more clinically useful than WR-2721.

Adenosine Triphosphate↗
PubMed1995

Failure of isradipine to reduce infarct size in mouse, gerbil, and rat models of cerebral ischemia.

BACKGROUND AND PURPOSE: The dihydropyridine L-type calcium channel blocker isradipine has been reported to exhibit neuroprotective properties in some, but not all, studies performed in the rat middle cerebral artery occlusion (MCAO) model. In the present study, we examined isradipine in several other models of focal and global ischemia: rat rose bengal, mouse MCAO, and gerbil bilateral carotid artery occlusion (BCAO). For comparison, a novel calcium channel blocker, SB201823A, that we have previously shown to be neuroprotective in rat and gerbil models was also examined in the mouse. METHODS: In the gerbil BCAO model, isradipine was administered at 2.5 mg/kg i.p. as a single dose 60 minutes after ischemia (n = 10). Corresponding controls received vehicle (n = 10), and sham-operated animals received no treatment (n = 6). Locomotor activity and histological assessments were made at 4 days after ischemia. In the rat photothrombotic occlusion model, isradipine was administered at 2.5 mg/kg i.p. as a single dose 60 minutes after ischemia (n = 10), and corresponding controls (n = 10) received vehicle. Histological assessment was made at 7 days after ischemia. In the mouse MCAO model, isradipine was also administered at 2.5 mg/kg i.p. as a single dose 60 minutes after ischemia. Histological assessments were made at 1 (n = 13), 2 (n = 9), and 4 (n = 9) days after ischemia. Vehicle numbers were n = 10, n = 6, and n = 8, respectively. Isradipine and SB201823A were also examined using a combined preischemia and postischemia regimen. Isradipine was administered at 2.5 mg/kg i.p. before occlusion, 1.25 mg/kg i.p. 1 hour after occlusion, 1.25 mg/kg i.p. 2 hours after occlusion, and 2.5 mg/kg twice a day for 3 days after occlusion (n = 16). Corresponding controls received vehicle at the same time points (n = 14). SB201823A was administered 30 minutes before occlusion, 30 minutes after occlusion, and twice daily for 3 days (n = 12). Corresponding controls received vehicle (n = 9). Histological assessment was performed at 4 days after ischemia. RESULTS: When given after ischemia, isradipine failed to affect lesion volume in both the rat and mouse models. In the gerbil, locomotor hyperactivity and hippocampal cell loss were unaffected. Given before and after ischemia in the mouse, isradipine was also ineffective, whereas SB201823A produced a significant reduction in lesion volume. CONCLUSIONS: The L-type calcium channel blocker isradipine was devoid of neuroprotective activity in focal and global models of cerebral ischemia in three species of normotensive animals. These results were compared with data for the novel calcium channel blocker SB201823A, which exhibited a significant effect after pre- and postocclusion administration in the mouse model of permanent focal ischemia.

Animals↗
PubMed1995

Thiazolidine prodrugs of cysteamine and cysteine as radioprotective agents.

The need for protection against the toxic effects of ionizing radiation comes from many different directions: occupational exposure, nuclear accidents, environmental sources and protection of normal tissue during the therapeutic irradiation of cancer. Sulfhydryl-containing compounds, including cysteamine and L-cysteine, have long been known to possess radioprotective properties, but their therapeutic utility is limited by their side effects at radioprotective doses. To avoid this drawback, thiazolidine prodrugs of cysteamine and L-cysteine were prepared by the condensation of each thioalmine with the aldose monosaccharides, D-ribose and D-glucose, producing RibCyst, GlcCyst, RibCys and GlcCys. The prodrugs were designed to liberate the parent thiolamine nonenzymatically, after ring opening and hydrolysis, which is then available to function as a radioprotective agent. Cysteamine's inherent toxicity, measured using Chinese hamster V79 cells growing in culture, was completely eliminated, even at concentrations as high as 25 mM, by providing the thiolamine in the form of a prodrug. Good protection against radiation-induced lethality was demonstrated by the cysteamine prodrugs using a clonogenic assay. Protection against radiation-induced DNA single-strand breaks, as measured by alkaline elution, was also shown by both RibCyst and GlcCyst; this activity was higher than that exhibited by either cysteamine or WR-1065. The L-cysteine prodrugs, RibCys and GlcCys, also possessed radioprotective abilities under most of the conditions studied. Protection against DNA damage was comparable between L-cysteine, WR-1065 and RibCys.

Animals↗
PubMed1994

Effects of peer review and editing on the readability of articles published in Annals of Internal Medicine.

OBJECTIVE: To measure the effect of the peer review and editorial processes on the readability of original articles. DESIGN: Comparison of manuscripts before and after the peer review and editorial processes. SETTING: Annals of Internal Medicine between March 1 and November 30, 1992. MANUSCRIPTS: One hundred one consecutive manuscripts reporting original research. MEASUREMENTS: Assessment of readability by means of two previously validated indexes: the Gunning fog index (units of readability in the fog index roughly correlate to years of education) and the Flesch reading ease score. Each manuscript was analyzed for readability and length on receipt and after it had passed through the peer review and editorial processes. Text and abstracts were analyzed similarly but separately. Mean readability scores were compared by two-tailed t tests for paired observations. RESULTS: Mean (+/- SD) initial readability scores of manuscripts and abstracts by the Gunning fog index were 17.16 +/- 1.55 and 16.65 +/- 2.80, respectively. At publication, scores were 16.85 +/- 1.42 and 15.64 +/- 2.42 (P = .0005 and P < .0001 for before-after differences, respectively). By comparison, studies of other print media showed scores of about 11 for the New York Times editorial page and about 18 for a typical legal contract. Similar changes were found for the Flesch scores. The median length of the manuscripts increased by 2.6% and that of the abstracts by 4.2% during the processes. CONCLUSIONS: The peer review and editorial processes slightly improved the readability of original articles and their abstracts, but both remained difficult to read at publication. Better readability scores may improve readership.

Manuscripts as Topic↗
PubMed1994

How do physicians talk with their patients about risks?

To describe the communication about risk between community-based physicians and their patients, the authors audiotaped 160 physician-patient encounters in the private practices of 19 physicians. Coding was done using a structured scheme to identify the presence of talk about risk of future illness, and to describe its characteristics. Patient understanding and satisfaction were assessed through an interview. Risk discussion occurred in 26% (95% CI 19%-33%) of the visits, quantitatively in two cases and specifically with respect to outcome in 48% (95% CI 40%-56%) of the visits. The patients initiated only 16% of this discussion but were, in general, satisfied with their care and the information they had received, but they had poor recall of the specifics of the discussion.

Communication↗
PubMed1994

'Tactile sensation': a new clinical sign during fine needle aspiration of breast lumps.

The tactile sensation (TS) felt during fine needle aspiration (FNA) of symptomatic breast abnormalities was recorded prospectively in 169 patients. TS was classified as malignant (if 'gritty'), or benign (if 'rubbery', 'soft' or 'fibrous'). This assessment was compared with fine needle aspiration cytology (FNAC) and the final diagnosis, to evaluate the clinical utility of TS. A 'gritty' TS was recorded in 55/59 cancers and 22/110 benign lesions (sensitivity 93.2%, specificity 80%). Comparison of TS and FNAC in 69 patients with definitive histopathology revealed complementary results (TS, sensitivity 88.9%, specificity 48.5%; FNAC, sensitivity 55.6%, specificity 100%). Combining the sensitivity of TS with that of FNAC increased the overall sensitivity to 97.2%. Recording TS during FNA of symptomatic breast lumps enhances diagnosis, and alerts the clinician to the possibility of an underlying carcinoma when FNAC fails to confirm malignancy.

Biopsy, Needle↗