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Cellular senescence is emerging as a key mechanism of age-related vascular endothelial dysfunction, but evidence in healthy humans is lacking. Moreover, the influence of lifestyle factors such as habitual exercise on endothelial cell (EC) senescence is unknown. We tested the hypothesis that EC senescence increases with sedentary, but not physically active, aging and is associated with vascular endothelial dysfunction. Protein expression (quantitative immunofluorescence) of p53, a transcription factor related to increased cellular senescence, and the cyclin-dependent kinase inhibitors p21 and p16 were 116%, 119%, and 128% greater (all P < 0.05), respectively, in ECs obtained from antecubital veins of older sedentary (60 ± 1 yr, n = 12) versus young sedentary (22 ± 1 yr, n = 9) adults. These age-related differences were not present (all P > 0.05) in venous ECs from older exercising adults (57 ± 1 yr, n = 13). Furthermore, venous EC protein levels of p53 ( r = −0.49, P = 0.003), p21 ( r = −0.38, P = 0.03), and p16 ( r = −0.58, P = 0.002) were inversely associated with vascular endothelial function (brachial artery flow-mediated dilation). Similarly, protein expression of p53 and p21 was 26% and 23% higher (both P < 0.05), respectively, in ECs sampled from brachial arteries of healthy older sedentary (63 ± 1 yr, n = 18) versus young sedentary (25 ± 1 yr, n = 9) adults; age-related changes in arterial EC p53 and p21 expression were not observed ( P > 0.05) in older habitually exercising adults (59 ± 1 yr, n = 14). These data indicate that EC senescence is associated with sedentary aging and is linked to endothelial dysfunction. Moreover, these data suggest that prevention of EC senescence may be one mechanism by which aerobic exercise protects against endothelial dysfunction with age. NEW & NOTEWORTHY Our study provides novel evidence in humans of increased endothelial cell senescence with sedentary aging, which is associated with impaired vascular endothelial function. Furthermore, our data suggest an absence of age-related increases in endothelial cell senescence in older exercising adults, which is linked with preserved vascular endothelial function. Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/aging-exercise-and-endothelial-cell-senescence/ .

Background and aims Limited data are available regarding fully covered metal stents in the management of malignant distal biliary strictures. The aim of this study was to evaluate the safety of a fully covered self-expanding metal stent (FCSEMS) with flared ends, in treating malignant biliary strictures. We report our long-term retrospective analysis from 6 centers. Methods A total of 260 patients (142 males, median age 68 y) underwent endoscopic retrograde cholangiopancreatography with placement of FCSEMS (WallFlex; Boston Scientific, Natick, MA) for the palliation of obstructive jaundice in the setting of pancreatic adenocarcinoma (169), metastatic disease (36), cholangiocarcinoma (23), ampullary cancer (19), or other (13). Patients were evaluated clinically in follow-up and biochemical tests of liver function were obtained. Data were recorded for the following variables: patient survival, duration of stent patency, the need for subsequent biliary intervention, and complications. Results A total of 266 FCSEMS were placed in 260 patients. There was a median survival of 100 days (range, 7 to 531 d). There was a mean follow-up of 134±118 days (range, 4 to 519 d). Biliary decompression was successful in 252 patients (97%). At the end of the study period, 121 were alive with a patent stent, 65 patients died with a patent stent, 40 patients were successfully bridged to surgery, 8 patients had their patent stent removed and had no need for further stenting, and 18 patients were lost to follow-up. Five patients who had a successfully placed FCSEMS were considered a failure due to the following reason: migration (2), cholangitis (1), stent occlusion (1), and removal for management of proximal biliary obstruction (1). Two additional patients experienced migration that did not require FCSEMS removal or replacement. Stent replacement was required in 10 patients, of whom 6 had a second FCSEMS placed. The remaining 4 were in the failure group and underwent replacement with either uncovered stents or plastic stents. Other complications, managed conservatively, included pain (2), postendoscopic retrograde cholangiopancreatography pancreatitis (4), fever (1), retroperitoneal perforation (1), and postsphincterotomy bleeding (1). The mean patency duration was 328 days (SE 19.04). The patency percentage was 83% at 3 months, 63% at 6 months, and 48.5% at 12 months. Conclusions In the management of malignant distal biliary strictures, the fully covered WallFlex stent has acceptable patency and complication rates. Further long-term prospective data are required to confirm this observation.

Service user involvement is essential for quality care in the Child and Adolescent Mental Health Services (CAMHS). This study was conducted to explore adolescents' and parents' experiences of CAMHS in relation to accessibility, approachability and appropriateness. This study used a descriptive qualitative design, and focus groups and single interviews were conducted with adolescents (n = 15) and parents (n = 32) from three mental health clinics. Data were analysed using thematic analysis. Accessing mental health services was a challenging experience for many parents and adolescents due to knowledge deficit, lack of information and limited availability of specialist services. Some parents and adolescents reported positive experiences while others reported negative experiences. They expressed a need for more information, involvement in decision making, flexible scheduling of appointments, school support and parent support groups. The nature and quality of the relationship with staff was critical to positive experience with the service; therefore, frequent changes of medical staff was disruptive. Mental health nurses can play a vital role in ensuring continuity, assessing adolescents' participation preferences and advocating for their information needs with other members of the interdisciplinary team.

Neuronal nicotinic acetylcholine receptors (nAChRs) at presynaptic sites can modulate dopaminergic synaptic transmission by regulating dopamine (DA) release and uptake. Dopaminergic transmission in nigrostriatal and mesolimbic pathways is vital for the coordination of movement and is associated with learning and behavioral reinforcement. We reported recently that the D2 DA receptor plays a central role in regulating the arbor size of substantia nigra dopaminergic neurons. Given the known effects of nAChRs on dopaminergic neurotransmission, we assessed the ability of the alpha4 nAChR subunit to regulate arbor size of dopaminergic neurons by comparing responses of wild-type and alpha4 nAChR subunit knockout [alpha4(-/-)] mice to long-term exposure to cocaine, amphetamine, nicotine, and haloperidol, and after substantia nigra neurotoxic lesioning. We found that dopaminergic neurons in adult drug-naive alpha4(-/-) mice had significantly larger terminal arbors, and despite normal short-term behavioral responses to drugs acting on pre- and postsynaptic D2 DA receptors, they were unable to modulate their terminal arbor in response to pharmacological manipulation or after lesioning. In addition, although synaptosome DA uptake studies showed that the interaction of the D2 DA receptor and the dopamine transporter (DAT) was preserved in alpha4(-/-) mice, DAT function was found to be impaired. These findings suggest that the alpha4 subunit of the nAChR is an independent regulator of terminal arbor size of nigrostriatal dopaminergic neurons and that reduced functionality of presynaptic DAT may contribute to this effect by impairing DA uptake.

1. We have characterised the effects of piperine, a pungent alkaloid found in black pepper, on the human vanilloid receptor TRPV1 using whole-cell patch-clamp electrophysiology. 2. Piperine produced a clear agonist activity at the human TRPV1 receptor yielding rapidly activating whole-cell currents that were antagonised by the competitive TRPV1 antagonist capsazepine and the non-competitive TRPV1 blocker ruthenium red. 3. The current-voltage relationship of piperine-activated currents showed pronounced outward rectification (25+/-4-fold between -70 and +70 mV) and a reversal potential of 0.0+/-0.4 mV, which was indistinguishable from that of the prototypical TRPV1 agonist capsaicin. 4. Although piperine was a less potent agonist (EC50=37.9+/-1.9 microM) than capsaicin (EC50=0.29+/-0.05 microM), it demonstrated a much greater efficacy (approximately two-fold) at TRPV1. 5. This difference in efficacy did not appear to be related to the proton-mediated regulation of the receptor since a similar degree of potentiation was observed for responses evoked by piperine (230+/-20%, n=11) or capsaicin (284+/-32%, n=8) upon acidification to pH 6.5. 6. The effects of piperine upon receptor desensitisation were also unable to explain this effect since piperine resulted in more pronounced macroscopic desensitisation (t(1/2)=9.9+/-0.7 s) than capsaicin (t(1/2)>20 s) and also caused greater tachyphylaxis in response to repetitive agonist applications. 7. Overall, our data suggest that the effects of piperine at human TRPV1 are similar to those of capsaicin except for its propensity to induce greater receptor desensitisation and, rather remarkably, exhibit a greater efficacy than capsaicin itself. These results may provide insight into the TRPV1-mediated effects of piperine on gastrointestinal function.

This research described in this paper examined the impact of varietal mixtures on pest management utilising a model system of partial insecticide applications. In six field experiments conducted in 1995 and 1996 in Igalaland, Kogi State, Nigeria varietal mixtures were simulated through the application of systemic insecticide (carbofuran or furathiocarb) to a pre-determined percentage of a cowpea ( Vigna unguiculata ) crop. The objective was to examine and compare the pest damage on untreated cowpea plants grown in plots in which varying percentages of the cowpea plants were treated with insecticide. A secondary objective was to determine whether action of the foliage pests influenced flower production. The results showed that the presence of insecticide-treated plants reduced the level of leaf damage by Ootheca mutabilis Sahlberg and the densities of Aphis craccivora Koch populations on untreated plants. The greater the percentage of insecticide-treated plants the greater this reduction on the untreated plants. Meanwhile, the number of flowers found on the untreated plants increased suggesting the foliage pest damage reduced flower production.

Field experiments were established in which cowpea (Vigna unguiculata Walpers) was treated with a series of partial insecticide (carbofuran) application treatments to simulate (susceptible/resistant) varietal mixtures and a series of inter-crops with soybean (Glycine max). Treatments were sampled for damage by the foliage pests Ootheca mutabilis Sahlberg and Aphis craccivora Koch and for flower production. The soybean is likely to have provided both a mechanical barrier to pest movement and disruption to O. mutabilis through volatile allelochemicals. The comparison between the two treatment types would suggest whether similar mechanisms were the cause of pest reductions observed in partial insecticide applications on cowpea. The results suggested that the inter-cropping with soybean was not as effective in managing pest populations as a partial insecticide application and could even increase pest numbers. Further examination of the data from the partial insecticide application treatments appeared to show that the pest infestation was lower on the untreated plants closest to the insecticide-treated plants. This could be as a result of pest redistribution onto insecticide-treated plants after initial colonisation. The implications of this, in terms of pest resistance management are discussed.

This paper presents the results of extensive experience in the development and promotion of tobacco-based insecticides for the control of field crop pests in Igalaland, Nigeria. A non-governmental organization (NGO), the Diocesan Development Services (DDS), became involved in the development of tobacco-based insecticides in the early 1990s, and facilitated a series of ‘on-farm’ trials between 1997 and 2000 designed to test the effectiveness of such insecticides for two crops that are particularly vulnerable to pest attack in Igalaland: cowpea (Vigna unguiculata) and maize (Zea mays). The results suggest that even crude tobacco formulations had a significant benefit on cowpea and maize yields relative to the absence of pest control, although commercial insecticides were more effective. However, while having advantages of cost and availability over commercial insecticides, tobacco-based products appear to have serious internal and external disadvantages that limit their widespread use, and some of these are discussed. It is concluded that while technical efficacy of botanicals is an important element, there are others such as the logistics of production and preparation that need to be considered. A better understanding of the balance between these factors and how context-specific they may be is required in order to maximize their adoption by farmers under ‘resource-poor’ conditions.

Uncertainty as to the functional role of the D(3) dopamine receptor, due primarily to a paucity of selective agonists or antagonists, is being addressed in mice with targeted gene deletion ("knockout") thereof. This study describes, for the first time, the phenotype of congenic D(3)-null mice. Initially, 129/Sv x C57BL/6 D(3)-null mice were backcrossed 14 times onto C57BL/6; they were then assessed using an ethologically based approach which resolves all topographies of behaviour within the mouse repertoire. The ethogram of D(3)-null mice, on comparison with wildtypes, was characterised by no alteration in any topography of behaviour over an initial period of exploration; subsequent assessment over several hours revealed only increased rearing among females due to delayed habituation. Low doses of the selective D(2)-like agonist RU 24213 (0.016-0.25 mg/kg) inhibited topographies of exploratory behaviour; this effect was diminished in D(3)-null mice only when investigated following prolonged habituation, and then only for certain topographies of behaviour, primarily sniffing and rearing. High doses of RU 24213 (0.1-12.5 mg/kg) induced stereotyped sniffing and "ponderous" locomotion, while the selective D(1)-like agonist SKF 83959 (0.016-2.0 mg/kg) promoted characteristic grooming syntax; these effects did not differ materially between the genotypes. When examined topographically on an essentially congenic C57BL/6 background (0.005% 129/Sv), the resultant phenotype indicated essential conservation of the mouse ethogram, high-dose D(2)-like stimulatory effects, and D(1)-like stimulatory effects in the absence of D(3) receptors. A role for D(3) receptors in inhibitory processes appeared topographically circumscribed and only when baseline levels of behaviour were low.

D(1A)-null mice were backcrossed over 14 generations into a C57BL/6 background to result in essential elimination (to

A novel system was used to assess the role of D 1 -like dopamine receptors in distinct topographies of orofacial movements in mice with congenic D 1A receptor knockout. Under spontaneous conditions, vertical jaw movements in wildtypes declined with time at a rate that was reduced in D 1A mutants, while horizontal jaw movements emerged progressively in wildtypes but not in D 1A mutants; tongue protrusions were absent in D 1A mutants, while incisor chattering was initially reduced in D 1A mutants but rose subsequently to reach the level of wildtypes. D 1A receptors exert a topographically specific role in regulating individual spontaneous orofacial movements, and these involve interactions with psychomotor processes which ‘sculpt’ behavioural change over time. The anomalous D 1 -like agonist SK&F 83959, which fails to stimulate, and indeed inhibits the stimulation of adenylyl cyclase induced by dopamine, readily stimulated vertical jaw movements, tongue protrusions and incisor chattering, and these response topographies were absent in D 1A mutants. These results suggest that D 1A receptors may exert some form of permissive role over orofacial topographies initiated via a novel, putative D 1 -like site not linked to adenylyl cyclase, or that some D 1A receptors might be coupled to a transduction system other than adenylyl cyclase.

A novel procedure for the assessment of orofacial movement topographies in mice was used to study, for the first time, the individual and interactive involvement of dopamine D 1 -like vs. D 2 -like receptors in their regulation. The dopamine D 1 -like receptor agonists A 68930 ([1 R ,3 S ]-1-aminomethyl-5,6-dihydroxy-3-phenyl-isochroman) and SK&F 83959 (3-methyl-6-chloro-7,8-dihydroxy-1-[3-methyl-phenyl]-2,3,4,5-tetrahydro-1 H -3-benzazepine) each induced vertical jaw movements with tongue protrusions and incisor chattering. The dopamine D 1 -like receptor antagonists SCH 23390 ([ R ]-3-methyl-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1 H -3-benzazepine) and BW 737C ([ S ]-6-chloro-1-[2,5-dimethoxy-4-propylbenzyl]-7-hydroxy-2-methyl-1,2,3,4-tetrahydroisoquinoline) antagonised these responses, while the dopamine D 2 -like receptor antagonist YM 09151-2 ( cis - N -[1-benzyl-2-methyl-pyrrolidin-3-yl]-5-chloro-2-methoxy-4-methylaminobenzamide) attenuated those to SK&F 83959 and released horizontal jaw movements. These findings suggest some role for a dopamine D 1 -like receptor that is coupled to a transduction system other than/additional to adenylyl cyclase, and for dopamine D 1 -like:D 2 -like receptor interactions, in the regulation of individual orofacial movement topographies in the mouse. This methodology will allow the use of knockout mice to clarify the roles of individual dopamine receptor subtypes in their regulation.

Yam rots caused by fungal pathogens (mostly Fusarium spp.) are a major cause of storage losses, and previous work has shown that fungal lesions were only found if there was pre-existing physical damage to the tuber. The general perception is that damage inflicted in the field prior to storage is far more important in this regard than damage caused during storage, and this has led to much research directed at the minimisation of field damage with relatively little work on the amelioration of insect damage during storage. This study examined whether insect damage inflicted on yam tubers during storage in specialised barns is an important agent in the incidence of fungal disease. It was found that treatment of tubers with insecticide dust (Actellic 2% Dust; ai=pirimiphos-methyl) significantly reduced fungal infections resulting from insect attack during storage. In addition, physical damage acquired during harvest appeared to be ameliorated by the insecticide, resulting in significantly fewer fungal lesions. The results suggest that insecticide treatment of yam tubers prior to storage could provide a relatively cheap and effective means of preservation.

UNSCEAR has estimated that 14 C discharges from the nuclear fuel reprocessing plant at Sellafield are responsible for about a quarter of the total global release of this radiologically important radionuclide. Reported discharges from the site have been based on direct monitoring of the effluent since 1978. Prior to that date, however, discharges have been estimated from the measurement of 14 C levels in the annual growth rings of a locally grown tree. In the present study, discharges prior to 1978 have been re-calculated based on new measurements of 14 C levels in tree rings. The results indicate that 14 C discharges from Sellafield prior to 1978 were significantly lower than previously thought, 124 TBq as opposed to 207 TBq. The total release of 14 C to the atmosphere from this site from the start of operations up to 1995 is now estimated to have been 244 TBq.

Background: Covered self-expanding metal stents are being used more frequently in benign biliary strictures (BBS). We report the results of a multicenter study with fully covered self-expanding metal stent (FCSEMS) placement for the management of BBS. Aim: To prospectively evaluate the efficacy and safety of FCSEMS in the management of BBS. Patients and Methods: Patients with BBS from 6 tertiary care centers who received FCSEMS with flared ends between April 2009 and October 2010 were included in this retrospective study. Patients and Methods: Efficacy was measured after removal of FCSEMS by evaluating stricture resolution on the basis of symptom resolution, imaging, laboratory studies, and/or choledochoscopy at removal. Safety profile was evaluated by assessing postprocedural complications. Results: A total of 133 patients (78, 58.6% males) with a mean age of 59.2±14.8 years with BBS received stents. Of the 133 stents placed, 97 (72.9%) were removed after a mean stent duration of 95.5±48.7 days. Stricture resolution after FCSEMS removal was as follows: postsurgical, 11/12 (91.6%); gallstone-related disease, 16/19 (84.2%); chronic pancreatitis, 26/31 (80.7%); other etiology, 4/5 (80.0%); and anastomotic strictures, 19/31(61.2%). Ninety-four patients were included in the logistic regression analyses. Patients who had indwelling stents for >90 days were 4.3 times more likely to have resolved strictures [odds ratio, 4.3 (95% confidence interval, 1.24-15.09)] and patients with nonmigrated stents were 5.4 times more likely to have resolved strictures [odds ratio, 5.4 (95% confidence interval, 1.001-29.29)]. Conclusions: FCSEMS for BBS had an acceptable rate of stricture resolution for postsurgical strictures, gallstone-related strictures, and those due to chronic pancreatitis. Predictors for stricture resolution include longer indwell time and absence of migration. Further study is warranted to assess long-term efficacy in a prospective manner with longer than 3-month time of stent indwelling time.

Using a novel system, the role of D2-like dopamine receptors in distinct topographies of orofacial movement was assessed in mutant mice with congenic D2 vs. D3 receptor knockout, and compared with findings in D1A mutants. Under spontaneous conditions, D2 mutants evidenced increased vertical jaw movements and unaltered horizontal jaw movements, with reductions in tongue protrusions and incisor chattering; in D3 mutants, only incisor chattering was reduced. Given previous evidence that D1A mutants show reduced horizontal but not vertical jaw movements, this indicates that apparent oppositional D1-like:D2-like interactions in the regulation of composited jaw movements may in fact reflect the independent actions of D2 receptors to inhibit vertical jaw movements and of D1A receptors to facilitate horizontal jaw movements. Effects of the D2-like agonist RU 24213 to exert greater reduction in horizontal than in vertical jaw movements were not altered prominently in either D2 or D3 mutants. The D1-like agonists A 68930 and SK&F 83959 induced vertical jaw movements, tongue protrusions, and incisor chattering; induction of tongue protrusions by A 68930 was reduced in D2 mutants. D2 receptors exert topographically specific regulation of orofacial movements in a manner distinct from their D1A counterparts, while D3 receptors exert only minor regulation of such movements. Fil: Tomiyama, Katsunori. Royal College of Surgeons in Ireland; Irlanda. Nihon University School of Dentistry; Japón Fil: Mcnamara, Fergal N.. Royal College of Surgeons in Ireland; Irlanda Fil: Clifford, Jeremiah J.. Royal College of Surgeons in Ireland; Irlanda Fil: Kinsella, Anthony. Dublin Institute of Technology; Irlanda Fil: Drago, John. Monash Medical Centre; Australia Fil: Fuchs, Sara. Weizmann Institute of Science; Israel Fil: Grandy, David K.. Oregon Health Sciences University; Estados Unidos Fil: Low, Malcolm J.. Oregon Health Sciences University; Estados Unidos Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Tighe, Orna. Royal College of Surgeons in Ireland; Irlanda Fil: Croke, David T.. Royal College of Surgeons in Ireland; Irlanda Fil: Koshikawa, Noriaki. Nihon University School of Dentistry; Japón Fil: Waddington, John L.. Royal College of Surgeons in Ireland; Irlanda

Congenic (10 backcrosses into C57BL/6J) mutants with targeted gene deletion of DARPP-32, a neuronal phosphoprotein regarded as an essential mediator of the biological effects of dopamine (DA), were assessed phenotypically using an ethologically based approach that resolves all topographies of behavior in the mouse repertoire. Over initial exploration, female, but not male, DARPP-32 mutants evidenced increased locomotion and decreased grooming, while a decrease in rearing seated was evident in mutants of both genders; continuing assessment over several hours did not reveal additional phenotypic effects. Following challenge with the nonselective DA receptor agonist apomorphine, low doses were associated with reduced levels of sniffing, grooming, total rearing, and rearing seated in DARPP-32 mutants relative to wildtypes; this would suggest some role for DARPP-32 in mediating the biological effects of presynaptic D(2)-like autoreceptor or inhibitory postsynaptic D(2)-like receptor activation. Following challenge with higher doses, while stereotyped sniffing and locomotion with chewing was largely unaltered, the additional murine response of Straub tail was essentially abolished in DARPP-32 mutants, indicating some specific involvement of DARPP-32 in mediating this topography of behavior; additionally, there were overall reductions in levels of sniffing, total rearing, rearing seated, and grooming in DARPP-32 mutants that were unrelated to the dose of apomorphine administered, indicating broader topographical effects following the stress of the injection procedure relative to more naturalistic conditions. The developmental absence of DARPP-32 following targeted gene deletion appears to be associated with compensatory processes that maintain certain topographies of spontaneous and agonist-induced DAergic function, while other topographies remain impaired.

Human lung cells exposed to pathogenic bacteria upregulate the production of mucin, the major macromolecular component of mucus. Generally this upregulation is beneficial for the host, however, in the lungs of cystic fibrosis patients, overproduction of mucin can lead to the plugging of pulmonary airways. Mucus plugging impedes airflow and creates an environment that is highly compartmentalized: those bacteria within the mucus layer are shielded from high doses of antibiotics whereas those outside the mucus are exposed. These conditions augment mutation rate and the development of drug resistance in bacteria that colonize the lungs of cystic fibrosis patients. While therapeutic inhibition of mucin induction would improve airflow and reduce antibiotic resistance in these patients, the challenge is to develop drugs that block excessive mucin production while leaving beneficial aspects of the response intact. To do this, we must understand the molecular mechanisms underlying mucin production. Here we review the signal transduction pathways that control mucin production in response to Gram-positive and Gram-negative bacteria.

1. In the absence of selective agonists and antagonists able to discriminate between individual members of the D1-like and D2-like families of dopamine receptor subtypes, functional parcellation has remained problematic. 2. ‘Knockout’ of these subtypes by targeted gene deletion offers a new approach to evaluating their roles in the regulation of behaviour. 3. Like any new technique, ‘knockout’ has associated with it a number of methodological limitations that are now being addressed in a systematic manner. 4. Studies on the phenotype of D1A/1, D1B/5, D2, D3 and D4 ‘knockouts’ at the level of spontaneous and agonist/antagonist-induced behaviour are reviewed, in terms of methodological issues, neuronal implications and potential clinical relevance. 5. Dopamine receptor subtype ‘knockout’ is a nascent technology that is now beginning to fulfill its potential. It is being complemented by more systematic phenotypic characterisation at the level of behaviour and additional, molecular biologically-based approaches.

We evaluated the effect of diclofenac sodium (Voltaren) drops on patients with hypoxia-induced corneal edema. Thirty age- and sex-matched subjects were randomly assigned to one of three groups. Members of each group received masked solutions of either Voltaren, Voltaren vehicle, or a non-preserved lubricant (Cellufresh) every 6 hours for 24 hours and then hourly for 2 hours immediately prior to inducing corneal edema in the experimental eye. Bilateral ultrasonic pachymetry was performed prior to applying a thick contact lens and light patch on the experimental eye of all subjects for 3 hours. The fellow eye served as the control. Following lens removal, bilateral corneal thickness was measured every 30 minutes. The percentage change in corneal swelling for each subject and group was calculated. The findings were also normalized to the control eye to minimize diurnal and individual variability. The results were plotted both as percentage change from hour 0 and percentage change normalized to the control eye. Corneal swelling ranged from 9-11% in all 3 groups, with recovery at 2-3 hours. No significant difference was found among the three groups (P0.05, ANOVA). There was a slight trend toward reduced thickness in the Cellufresh group, but this was not statistically significant. Voltaren does not appear to have an effect on the hypoxia-induced corneal edema associated with the production of arachidonic acid pathway metabolites.

Extracts of tissue showed that prostatic carcinomas contain less leucine aminopeptidase activity than benign prostatic hyperplasia. This is true when activity is expressed as specific activity (P = 0.0033), specific activity/% epithelium (P = 0.0007), activity/wet weight of tissue (P = 0.0028), or activity/wet weight of tissue/% epithelium (P = 0.0005). Almost all histochemically demonstrable activity is located in the epithelium. Enzymatic activities in extracts and in histochemical preparations showed similar differences between carcinoma and benign prostatic hyperplasia and were related (R = -0.38, P = 0.0400) to Gleason's grades. The transurethrally resected prostate cancers studied contained no well-differentiated tumors and a high proportion of poorly differentiated tumors. Histochemical activity is absent in most prostatic carcinomas and decreased in others. This observation is particularly interesting in view of the growing knowledge of tumor suppressor genes.

Obtaining venous access continues to be one of the most difficult problems faced by a physician caring for the pediatric patient in cardiac arrest. Our study examined the use of the intraosseous route (through the bone) to obtain venous access for sodium bicarbonate administration in a cardiac arrest model. Ventricular fibrillation was induced in 23 domestic swine. Cardiopulmonary resuscitation was performed for five minutes and sodium bicarbonate (1 mEq/kg) was administered through a peripheral IV line (n = 6), a central IV line (n = 5), or intraosseously (n = 6). Controls (n = 6) did not receive bicarbonate. Blood pH was sampled every two minutes for 30 minutes from the right ventricle, left ventricle, and femoral artery. An analysis of variance revealed that the central and intraosseous routes were significantly different (P less than .05) from the peripheral group, and that all three groups were significantly different (P less than .05) from the control. Pathology studies revealed only minor damage to bone when sodium bicarbonate was administered intraosseously. These data demonstrate that the intraosseous route is a rapid and effective alternative for venous access in a cardiac arrest model.