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Biomedical subjects

J J Smith

Publications and source records attributed to J J Smith.

At least 37 records · Page 2Linked to original sources

Major colorectal cancer resection should not be denied to the elderly.

AIMS: Adjuvant therapy after surgery for colorectal cancer is often denied to the elderly for various reasons. This study was to determine morbidity and mortality risk after surgery in the elderly and whether this is affected by adjuvant therapy. METHODS: Data were collected prospectively and entered on a database for all patients undergoing resection of colorectal cancer between January 1994 and July 2000. A total of 304 patients were included, 65 aged 80 years and over. RESULTS: There were 84 deaths, 21 (30%) in the over 80s, and 63 (26%) in the under 80s (P=0.51). The 'in-hospital' mortality was 10.1% in the over 80s and 3.8% in the under 80s (P=0.056). In the over 80s the colon was more affected than the rectum (P=0.002). The over 80s were less likely to be offered adjuvant therapy, 7.2% vs 42.1% (P<0.001). The 5 year survival (all-cause mortality) in the over 80s was 58.5% and 47.6% in the under 80s (P=0.25). Cox's regression analysis of all patients identified the following factors to be independently related to overall survival: age>80 years, post-operative leak, increasing Dukes stage and distant recurrence of disease. CONCLUSION: This study has demonstrated that surgery should not be denied to elderly patients with colorectal cancer as despite a higher post-operative morbidity and mortality rate and with the absence of adjuvant therapy, favourable long-term outcome can be achieved by resectional surgery alone.

Adult↗

Randomised trial of pre-operative colour duplex marking in primary varicose vein surgery: outcome is not improved.

OBJECTIVE: the ability of colour duplex to accurately locate incompetent venous sites has been widely published; its value in pre-operative marking in simple primary varicose vein surgery is evaluated in this study. DESIGN OF STUDY: prospective randomised controlled trial. SETTING: regional vascular service, hospital patients. SUBJECTS: consecutive patients (149) undergoing primary varicose vein surgery where the only difference was one group of patients received duplex marking prior to surgery. Six weeks and 12 months post-operatively all patients had a colour duplex scan to determine the accuracy of surgery and the presence of residual/recurrent varicose veins and completed the Aberdeen, SF-36, and EuroQol quality of life questionnaires. INTERVENTIONS: varicose vein surgery. MAIN OUTCOME MEASURES: Duplex evidence of venous incompetence, quality of life measures using the SF-36 and Aberdeen Varicose Veins Questionnaire. RESULTS: pre-operative marking of primary varicose veins by skilled duplex ultrasonography does not improve the accuracy or recurrence rate following surgery. Quality of life improved significantly following surgery in both groups, however there was no difference in this improvement between the groups. CONCLUSION: the trial has not demonstrated any additional benefit of pre-operative colour duplex marking over that of clinical and hand held Doppler marking in terms of satisfactory varicose vein surgery performance at 6 weeks or 12 months in patients with primary varicose veins of the long saphenous system. It role in the short saphenous system is less clear.

Female↗

Trimethoprim-sulfamethoxazole (TMP-SMZ) dose escalation versus direct rechallenge for Pneumocystis Carinii pneumonia prophylaxis in human immunodeficiency virus-infected patients with previous adverse reaction to TMP-SMZ.

Trimethoprim-sulfamethoxazole (TMP-SMZ) is the most effective Pneumocystis carinii pneumonia (PCP) prophylactic agent, but adverse reactions are common among human immunodeficiency virus (HIV)-infected patients and limit its use. This randomized, double-blind controlled trial compared 2 methods of TMP-SMZ reintroduction, 6-day dose escalation and direct rechallenge, for PCP prophylaxis in HIV-infected patients who had experienced previous treatment-limiting reactions. The primary end point was the ability to take single-strength TMP-SMZ daily for 6 months. Seventy-five percent of the dose-escalation group and 57% of the direct-rechallenge group continued to receive daily single-strength TMP-SMZ for 6 months (P= .014). Among premature discontinuations, 58% of the dose-escalation group and 70% of the direct-rechallenge group were due to adverse reactions. None of these reactions was serious. This study provides evidence that it is possible to successfully reintroduce TMP-SMZ to a significant proportion of HIV-infected patients who have experienced mild-to-moderate treatment-limiting adverse reactions.

Adult↗

A role for the peroxin Pex8p in Pex20p-dependent thiolase import into peroxisomes of the yeast Yarrowia lipolytica.

Peroxins are proteins required for peroxisome assembly. The cytosolic peroxin Pex20p binds directly to the beta-oxidation enzyme thiolase and is necessary for its dimerization and peroxisomal targeting. The intraperoxisomal peroxin Pex8p has a role in the import of peroxisomal matrix proteins, including thiolase. We report the results of yeast two-hybrid analyses with various peroxins of the yeast Yarrowia lipolytica and characterize more fully the interaction between Pex8p and Pex20p. Coimmunoprecipitation showed that Pex8p and Pex20p form a complex, while in vitro binding studies demonstrated that the interaction between Pex8p and Pex20p is specific, direct, and autonomous. Pex8p fractionates with peroxisomes in cells of a PEX20 disruption strain, indicating that Pex20p is not necessary for the targeting of Pex8p to peroxisomes. In cells of a PEX8 disruption strain, thiolase is mostly cytosolic, while Pex20p and a small amount of thiolase associate with peroxisomes, suggesting the involvement of Pex8p in the import of thiolase after docking of the Pex20p-thiolase complex to the membrane. In the absence of Pex8p, peroxisomal thiolase and Pex20p are protected from the action of externally added protease. This finding, together with the fact that Pex8p is intraperoxisomal, suggests that Pex20p may accompany thiolase into peroxisomes during import.

Acetyl-CoA C-Acetyltransferase↗

Cardiologic problems in the post acute ventilated patient.

Chronically critically ill patients who develop acute respiratory failure commonly have complicating cardiac pathology that may or may not be evident at initial evaluation. The acute coronary syndromes should be excluded in all patients presenting with respiratory failure. Cardiac rhythm disturbances are common and should be actively investigated and treated in all critically ill patients. Heart failure is common in the chronically critically ill patient but usually responds to early diagnosis and prompt treatment. Finally, cardiogenic shock carries a poor prognosis in most patient subsets except when it is caused by cardiac tamponade. The intensivist must be vigilant for cardiac pathology complicating the recovery of patients with acute respiratory illness and initiate the search for correctable problems that may precipitate further episodes of respiratory insufficiency.

Combined Modality Therapy↗

Heart failure etiology affects peripheral vascular endothelial function after cardiac transplantation.

OBJECTIVES: The goal of this study was to examine the effect of heart failure etiology on peripheral vascular endothelial function in cardiac transplant recipients. BACKGROUND: Peripheral vascular endothelial dysfunction occurs in patients with heart failure of either ischemic or nonischemic etiology. The effect of heart failure etiology on peripheral endothelial function after cardiac transplantation is unknown. METHODS: Using brachial artery ultrasound, endothelium-dependent, flow-mediated dilation (FMD) was assessed in patients with heart failure with either nonischemic cardiomyopathy (n = 10) or ischemic cardiomyopathy (n = 7), cardiac transplant recipients with prior nonischemic cardiomyopathy (n = 10) or prior ischemic cardiomyopathy (n = 10) and normal controls (n = 10). RESULTS: Patients with heart failure with either ischemic cardiomyopathy or nonischemic cardiomyopathy had impaired FMD (3.6 +/- 1.0% and 5.1 +/- 1.2%, respectively, p = NS) compared with normal subjects (13.9 +/- 1.3%, p < 0.01 compared with either heart failure group). In transplant recipients with antecedent nonischemic cardiomyopathy, FMD was markedly higher than that of heart failure patients with nonischemic cardiomyopathy (13.0 +/- 2.4%, p < 0.001) and similar to that of normal subjects (p = NS). However, FMD remained impaired in transplant recipients with prior ischemic cardiomyopathy (5.5 +/- 1.5%, p = 0.001 compared with normal, p = 0.002 vs. transplant recipients with previous nonischemic cardiomyopathy). CONCLUSIONS: Peripheral vascular endothelial function is normal in cardiac transplant recipients with antecedent nonischemic cardiomyopathy, but remains impaired in those with prior ischemic cardiomyopathy. In contrast, endothelial function is uniformly abnormal for patients with heart failure, regardless of etiology. These findings indicate that cardiac transplantation corrects peripheral endothelial function for patients without ischemic heart disease, but not in those with prior atherosclerotic coronary disease.

Adult↗

Development of a PCR test for the detection of Curtobacterium flaccumfaciens pv. flaccumfaciens.

A chromosomal DNA library of the bacterial pathogen of bean, Curtobacterium flaccumfaciens pv.flaccumfaciens NCPPB 559 was constructed in the plasmid pGEM-7Zf(+). Several clones were identified that hybridised to all Curtobacterium flaccumfaciens pathovars including: C. f betae, C. f flaccumfaciens, C. f oortii, C. f. poinsettiae and, in addition, to some strains of Clavibacter michiganensis subsp. insidiosus and Clavibacter michiganensis subsp. One of these clones (pPMP-26), after subsequent digestion with restriction endonucleases EcoRI/SacI, yielded a fragment of approximately 0.2 Kb (pPMP-26D) that hybridised specifically to C. f flaccumfaciens and not to any of the other plant pathogenic members of the order Actinomycetales or any of the other prokaryotic bean pathogens tested. This fragment was subcloned and sequenced, analysis of the resultant 198 bp sequence showed that no significant homology existed with any other sequence currently deposited in public databases. Further analysis of these data facilitated the design of PCR primers which were subsequently tested against a wide range of plant pathogenic actinomycetes and other prokaryotic bean pathogens. Results show that these primers are highly specific for all strains of C. f flaccumfaciens with no cross-reaction to strains from any other bacterial taxa tested.

Actinomycetales↗

Relaxation to authentic nitric oxide and SIN-1 in rat isolated mesenteric arteries: variable role for smooth muscle hyperpolarization.

Authentic nitric oxide (NO; 0.1 - 10 micromoles) caused transient, dose-dependent relaxation of phenylephrine-induced tone without changing membrane potential in mesenteric arteries. Larger doses, above 10 micromoles, did not evoke more relaxation (maximal relaxation to 150 micromoles NO in denuded arteries, 69+/-7%, n=8) but stimulated muscle hyperpolarization (maximum 19+/-3 mV, n=5). The soluble guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 microM), abolished relaxation to low doses of NO (n=4), but did not modify hyperpolarization with higher doses of NO (n=4). The potassium channel blocker charybdotoxin (ChTX; 50 nM) abolished hyperpolarization to high doses of NO and significantly reduced the maximal relaxation (to 43+/-6%, n=4; P<0.01). ODQ and ChTX together abolished tension and membrane potential change to all doses of NO (n=4). All relaxations to 3-morpholino-sydnonimine (SIN-1; 0.01 - 10 microM) were associated with hyperpolarization. When the endothelium was intact, ChTX inhibited hyperpolarization and relaxation to SIN-1 (n=5), while iberiotoxin (IbTX; 50 nM) or 4-aminopyridine (4-AP; 500 microM) reduced relaxation by 40% and 20%, respectively and by 80% in combination (n=6 in each case). In denuded arteries, relaxation to SIN-1 was unaffected by either ChTX or ODQ alone, but abolished by the inhibitors together (n=6). Alone, 4-AP did not alter relaxation, but in the presence of ODQ it reduced the maximal response by around 45% (n=6; P<0.01). 4-AP, ODQ and IbTX together inhibited relaxation to SIN-1 by 75% (n=6; P<0.01). Therefore, cyclic guanosine 3',5'-monophosphate (cyclic GMP)-independent smooth muscle hyperpolarization, possibly involving direct activation of calcium-activated and voltage-sensitive potassium channels, contributes to relaxation evoked by authentic NO and SIN-1. However, the importance of each pathway depends on the source of NO and with SIN-1 the relative contribution from each pathway is modified by the endothelium.

4-Aminopyridine↗

Conserved vertebrate chromosome segments in the large salamander genome.

Urodele amphibians (salamanders) are important models for embryological, physiological, and natural history research and are also a biomedically important group because they are the only vertebrates capable of regenerating entire organ systems. To enhance the utility of salamanders for biomedical research and for understanding genome evolution, genetic linkage analysis was used to identify chromosome segments that are homologous between ambystomatid salamanders and distantly related vertebrate model organisms. A total of 347 loci (AFLPs, RAPDs, and protein-coding loci) were mapped using an interspecific meiotic mapping panel (Ambystoma mexicanum and A. tigrinum tigrinum; family Ambystomatidae). Genome size in Ambystoma was estimated to be 7291 cM, the largest linkage map estimate reported for any organism. However, the relatively large size of the salamander genome did not hinder efforts to map and identify conserved syntenies from a small sample of 24 protein-coding loci. Chromosomal segments that are conserved between fishes and mammals are also conserved in these salamanders. Thus, comparative gene mapping appears to be an efficient strategy for identifying orthologous loci between ambystomatid salamanders and genomically well-characterized vertebrate model organisms.

Animals↗

Regulation of medical devices in radiology: current standards and future opportunities.

Today's radiology community depends heavily on cutting-edge diagnostic and therapeutic medical devices to serve patients. These products are regulated by the U.S. Food and Drug Administration (FDA) under a system that grants marketing approval for only those indications for which the safety and effectiveness have been established. Although this complex system is the result of a societal decision to ensure device safety and effectiveness, it has the potential to delay product marketing and impede innovation. Medical device regulation recently has undergone major changes with the enactment of the Food and Drug Administration Modernization Act of 1997 (FDAMA), legislation that is intended to increase system efficiency while retaining the requirement of safety and effectiveness. However, many of the envisioned improvements cannot occur without cooperative interaction between stakeholders in the device development process, including the FDA and the clinical medicine community. The radiology field must continue to build on its strong history of productive dialogue with the FDA to transform the legislative vision of FDAMA into regulatory reality. Such action will ensure timely access to the new device technologies that are necessary for the growth of our specialty and the effective care of our patients.

Device Approval↗

Native Vaccinium spp. and Gaylussacia spp. infested by Rhagoletis mendax (Diptera: Tephritidae) in the Great Lakes Region: a potential source of inoculum for infestation of cultivated blueberries.

In this study, we addressed the question of whether or not native stands of blueberry (Vaccinium spp.) and/or huckleberry (Gaylussacia spp.) support populations of blueberry maggot, Rhagoletis mendax Curran, in the Great Lakes region. Infestation of commercial blueberries by the blueberry maggot, R. mendax, is a serious problem in many areas where blueberries are grown. In the past 10-20 yr, commercial bighbush blueberry, Vaccinium corymbosum L., production has expanded into places such as southern Ontario and southern Quebec where blueberry maggot had not previously been reported. In the mid-1990s, isolated infestations of commercial highbush blueberry were reported in southern Ontario. Because R. mendax was not considered endemic to that area, it was widely assumed that the pests had come into the fields via movement from exotic localities. Here we present an alternative hypothesis, that the blueberry maggots infesting newly established highbush plantations are derived from native blueberries growing in the vicinity. To test this hypothesis, in 1997-1999, we sampled potential native hosts for R. mendax (Vaccinium spp. and Gaylussacia spp.) from 31 localities in the Great Lakes region, primarily in Michigan and Ontario. R. mendax was reared from fruits of native hosts collected at four sites in Michigan and one site each in Ontario, Indiana, and Ohio. V. corymbosum was the predominant host infested, with infestation of this host observed at five of the seven sites. However, two huckleberry species [Gaylussacia baccata (Wangenheim) K. Koch, and Gaylussacia dumosa (Andersson) Torrey & Gray] had the highest rates of infestation that we observed (25.4 and 17.6%, respectively). These data represent the first published reports of R. mendax infesting native host plants in the Great Lakes region, and support the hypothesis that infestations observed in commercial fields may have originated from infested native host plants.

Animals↗

cAMP stimulation of HCO3- secretion across airway epithelia.

To test for the presence of HCO(3)(-) transport across airway epithelia, we measured short-circuit current in primary cultures of canine and human airway epithelia bathed in a Cl(-)-free, HCO(3)(-)/CO(2)-buffered solution. cAMP agonists stimulated a secretory current that was likely carried by HCO(3)(-) because it was absent in HCO(3)(-)-free solutions. In addition, the cAMP-stimulated current was inhibited by the carbonic anhydrase inhibitor, acetazolamide, and by the apical addition of a blocker of cystic fibrosis transmembrane conductance regulator (CFTR), diphenylamine-2-carboxylate. The current was dependent on Na(+) because it was inhibited by removing Na(+) from the submucosal solution and by inhibition of the Na(+)-K(+)-ATPase with ouabain. The cAMP-stimulated current was absent in cystic fibrosis (CF) airway epithelia. These data suggest that cAMP agonists can stimulate HCO(3)(-) secretion across airway epithelia and that CFTR may provide a conductive pathway for HCO(3)(-) movement across the apical membrane.

Animals↗