Biomedical subjects
Publications and source records attributed to S Davis.
Grommet insertion is one of the commonest surgical procedures performed in the UK. We have come across three cases in which grommets have displaced medially in the middle ear after establishing a satisfactory post-insertion position. We suggest that an abnormally long myringotomy incision and improper placement of the grommet are responsible for this unwanted outcome.
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The risk of lung and breast cancer is significantly increased after therapy for Hodgkin's disease (HD), but there are few data that describe the molecular profiles of these tumors. We investigated the genetic abnormalities in second primary lung (n = 19) and breast cancers (n = 19) that follow therapy for HD ("post-HD cancers") and compared these with changes observed in corresponding tumor types (57 lung and 20 breast cancers) arising in the general population ("sporadic cancers"). DNA obtained from archival tissues was examined using PCR-based analyses for loss of heterozygosity and microsatellite alterations (MAs) at several chromosomal regions, TP53 and K-ras gene mutations, and frameshift mutations at minisatellite sequences at the coding regions of several genes (TGF-betaRII, IGFIIR, BAX, hMSH6, and hMSH3). The occurrence of loss of heterozygosity at all chromosomal regions taken together and frequencies at most individual areas were similar for the post-HD and sporadic cancers for both lung and breast sites. The overall frequency of MAs in the post-HD tumors was substantially greater (lung, 2.4-fold, P = 0.004; breast, 4.2-fold, P = 0.16) than that in the respective sporadic cancers. No differences in the pattern of TP53 and K-ras mutations were detected between post-HD and sporadic cancers. No mutations were detected at the minisatellite sequences examined. MAs, which reflect widespread genomic instability, occur at greatly increased frequency in post-HD lung and breast cancers. Although the mechanisms underlying the development of increased MAs are unknown, they have been associated with immunosuppression and radiation exposure. Future research should address the role that MAs, as well as other influences, may play in the development of neoplasias that occur after therapy for HD.
Revascularization of an ischemic lower extremity is associated with high morbidity (20-30%) and perioperative mortality (10-20%) regardless of the mode of intervention, surgical or thrombolytic, considered to be due to polymorphonuclear (PMN) activation and mediator release. In this study, the safety and feasibility of cell-free extracorporeal perfusion of the limb with a solution designed to minimize both local and systemic injury was tested. Methods. Patients with severe limb ischemia (sensory/motor loss, rest pain/gangrene) were studied prospectively by random assignment into the treatment arm (n = 14) or control arm (n = 21). Surgical management consisted of restorative procedure, thrombectomy or embolectomy (n = 21), or reconstruction (n = 14). Reperfusion of the ischemic limb was achieved with hypertonic, hyperoncotic perfusate containing anti-oxidants delivered via the arterial tree (mean volume 1835 +/- 824 ml) with initial venous drainage (mean volume 775 +/- 263 ml) in the restorative group. Means were compared by paired t test. Results. No adverse systemic effects were detected after limb perfusion (electrolytes, coagulation, platelet function, CBC). Rapid lactate wash-out was observed within 30 min of perfusion (preperfusion 3.2 +/- 4.1 mM, 30 min postperfusion 0.7 +/- 0.71 mM, P < 0.01). Blunting of PMN activation was shown by chemiluminescence (CL) analysis (preischemic CL: 0.68 +/- 0.2; 30 min CL: 0.47 +/- 0. 2; P < 0.013). F2-isoprostanes, a marker of free radical-mediated systemic lipid peroxidation, were significantly reduced in patients treated with study perfusion method (70.55 +/- 39.54 versus control 194.38 +/- 25.24, P < 0.005). Mortality with treatment was 0/14 versus 5/21 in the control. Complication frequency: MI 0/14 vs 3/21; renal 0/14 vs 1/21; leg edema 1/14 vs 5/21; amputations 2/14 vs 1/21. Conclusion. Modification of limb perfusion in patients with severe limb ischemia, using our simple and rapid (15-20 min) method provides beneficial systemic effects.
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The angiopoietins have recently joined the members of the vascular endothelial growth factor family as the only known growth factors largely specific for vascular endothelium. The angiopoietins include a naturally occurring agonist, angiopoietin-1, as well as a naturally occurring antagonist, angiopoietin-2, both of which act by means of the Tie2 receptor. We now report our attempts to use homology-based cloning approaches to identify new members of the angiopoietin family. These efforts have led to the identification of two new angiopoietins, angiopoietin-3 in mouse and angiopoietin-4 in human; we have also identified several more distantly related sequences that do not seem to be true angiopoietins, in that they do not bind to the Tie receptors. Although angiopoietin-3 and angiopoietin-4 are strikingly more structurally diverged from each other than are the mouse and human versions of angiopoietin-1 and angiopoietin-2, they appear to represent the mouse and human counterparts of the same gene locus, as revealed in our chromosomal localization studies of all of the angiopoietins in mouse and human. The structural divergence of angiopoietin-3 and angiopoietin-4 appears to underlie diverging functions of these counterparts. Angiopoietin-3 and angiopoietin-4 have very different distributions in their respective species, and angiopoietin-3 appears to act as an antagonist, whereas angiopoietin-4 appears to function as an agonist.
Simple models for the integration of a selectively neutral transgene into a feral population, by stocking of transgenic individuals, are developed. The impact of stocking individuals having multiple unlinked homozygous locations of the transgene is quantified. Initially it is assumed that there is no overlap between successive generations but a more general model for species having discrete overlapping generations is also developed. The primary application for this work is biological control. It is found that the integration of a transgene is considerably quickened by stocked transgenics carrying the transgene at multiple sites.
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BACKGROUND: Recent trials utilizing single anticytokine agents have shown no consistent survival benefit in improving the outcome of sepsis. Since an entire cascade of mediators contributes to the underlying pathophysiology, it is not surprising that monotherapy has proven unsuccessful. The purpose of this study was to measure the effects of attenuating tumor necrosis factor (TNF)alpha early in sepsis. METHODS: Three groups of Sprague-Dawley rats were studied. All animals were infused with live Escherichia coli, with group I and group II rats additionally receiving a matrix metalloproteinase inhibitor. Serum levels of TNFalpha, interleukin (IL)-6, malondialdehyde (MDA), and lipid hydroperoxide (LOOH) were compared. RESULTS: TNFalpha showed a significant decrease, yet IL-6, MDA, and LOOH (markers of sepsis) levels remained abnormally elevated. CONCLUSION: Despite significantly attenuating TNFalpha, the septic response continued. This supports the concept that in sepsis, monotherapy directed at attenuating a single cytokine cannot overcome the tissue-damaging effects of an entire cascade of mediators.
PURPOSE: To investigate the effects separately and together of (a) shortening overall treatment time and (b) giving concurrent carboplatin in patients having radical radiotherapy for inoperable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between April 1989 and May 1995, 204 patients with medically inoperable or technically unresectable NSCLC localised to the primary site and regional lymph nodes were randomised to receive one of four treatments using a 2 x 2 factorial design: standard radiotherapy, 60 Gy in 30 fractions in 6 weeks (R6); accelerated radiotherapy, 60 Gy in 30 fractions in 3 weeks (R3); standard radiotherapy as in R6 with carboplatin 70 mg/m2/day for 5 days during weeks 1 and 5 of radiotherapy (R6C); accelerated radiotherapy as in R3 with carboplatin 70 mg/m2/day for 5 days during week 1 of radiotherapy (R3C). RESULTS: The estimated median survival of all randomised patients was 15.7 months and estimated 2-year survival was 31%. The longest survival was seen in patients randomised to R6C (median 20.3 months, 41% surviving at 2 years) but there were no statistically significant differences between treatment arms or treatment factors (carboplatin versus no carboplatin, accelerated versus conventional radiotherapy). Haematological toxicity was significantly greater in patients treated with carboplatin and oesophageal toxicity was significantly greater and more protracted in patients treated with accelerated radiotherapy. CONCLUSIONS: This study failed to show a significant survival advantage for any of the treatment arms or factors. Halving overall treatment time resulted in significantly greater oesophageal toxicity with no suggestion of a survival advantage.
PURPOSE: A plasmid-based gene expression system was complexed with protective, interactive, and non-condensing (PINC) polymer system and administered with Medi-Jector, a needle-free injection device (NFID), to achieve high and sustained levels of antigen-specific antibodies in blood circulation. METHODS: Human growth hormone (hGH) or bacterial beta-galactosidase gene expression plasmids driven by a cytomegalovirus (CMV) promoter were formulated in saline or complexed with a PINC polymer, polyvinylpyrrolidone (PVP), and intramuscularly or subcutaneously administered into dogs and pigs using a 22-gauge needle or a NFID. The hGH-specific IgG titers in serum were measured by an ELISA. Beta-galactosidase expression was measured in injected muscles by an enzymatic assay or immunohistochemistry. The effect of NFID on DNA stability and topology was assessed by gel electrophoresis. RESULTS: Intramuscular (i.m.) or subcutaneous (s.c.) injection of a hGH expression plasmid pCMV-hGH (0.05-0.5 mg/kg) in dogs and pigs elicited antigen-specific IgG antibody titers to expressed hGH. With both routes of injection, pDNA delivery by a NFID was superior to pDNA injection by needle. The magnitude of hGH-specific IgG titers with NFID was 15-20-fold higher than needle injection when pDNA was complexed with PVP, and only 3-4-fold higher with pDNA in saline. The transfection efficiency in the injected muscle, as measured by beta-galactosidase expression, following i.m. injection of pCMV-betagalactosidase/PVP, was not significantly different between needle and NFID-injected groups. CONCLUSIONS: These data demonstrate that the combination of pDNA/ PVP complexes and a NFID act synergistically to achieve high and sustained levels of antigen-specific IgG response to expressed antigen. This gene delivery approach may offer advantage over needle injection of naked DNA for the development of genetic vaccines.
BACKGROUND: The cytokine receptor CD30 is an activation marker of T cells which preferentially associates with the production of the TH2 cytokine IL-4. Therefore, it may potentially be a candidate marker for atopic disorders and a target molecule for new therapeutic approaches. OBJECTIVE: To test the hypothesis that elevated levels of soluble CD30 (sCD30) are significantly associated with atopic disorders after adjustment for other predictors of atopy. METHODS: The presence of elevated sCD30 (> or = 20 U/mL) in atopic disorders was evaluated in a nested case-control study. Cases (n = 60) were blood donors with specific IgE antibodies, total serum levels of IgE > or = 100kU/L and presence or history of allergic symptoms. Controls (n = 59) were blood donors without presence or history of allergic symptoms and serum levels of IgE < 50 kU/L. sCD30 was determined from serum samples by an enzyme-linked immunosorbent assay. Odds ratios (OR) and confidence intervals (CI) were calculated from logistic regression coefficients. RESULTS: Mean sCD30 levels for cases were 75 U/mL (SD 110U/mL) as compared with 35 U/mL (SD 59 U/mL) for controls. Serum levels of sCD30 were elevated in 65% of cases and 32% of controls (OR 3.9, 95% CI 1.8-8.4). The odds ratio for elevated sCD30 as a predictor of atopic disorders slightly decreased to 3.7 after controlling for smoking, age and gender. Blood eosinophilia which was a strong predictor of atopy (OR 11.7) was a weak confounder of the association between sCD30 levels and atopic disorders. Family history of allergy, another strong predictor of atopy (OR 8.6), did not confound the association. CONCLUSIONS: The results are consistent with the hypothesis that CD30 is involved in the pathogenesis of atopic disorders independent of eosinophilia and family history of allergy.
OBJECTIVE: To describe and understand variations in cigarette brand preferences between adolescents from varying ethnic and gender groups around the US. DESIGN: A qualitative study where adolescents, both smokers and nonsmokers, were interviewed individually in depth. SETTING: Schools and recreation centers in four sites: urban Maryland (Baltimore), urban Texas (Houston), rural Alabama and rural New Mexico. PARTICIPANTS: 121 adolescent volunteers 13-19 years of age, representing African American, white, American Indian and Hispanic ethnic groups, from both genders. RESULTS: Considerable geographic and ethnic variation exists in terminology used by youth to refer to cigarettes and to their use. Clear patterns in brand preference by ethnic group were found that follow patterns of targeted marketing by ethnicity. White teens preferred Marlboro brand cigarettes, while African-American teens who smoke preferred Newports. Hispanic and American Indian teens were more likely to smoke Marlboro or Camel cigarettes. Hispanic teens were most likely to mention low price as a reason for choosing a particular brand or to state that the brand does not matter. Tobacco advertisements targeting ethnic groups and the use of promotional items to encourage teen smoking were also recognized as factors influencing brand preferences. CONCLUSIONS: These findings have implications for the design of intervention programs aimed at curbing teen smoking. When working with teens who already smoke, using youth language to target messages at perceived characteristics of commonly used brands may be more effective and meaningful than talking about cigarette use in general. Another implication of this work is to shed light on what impact an advertising ban would have on teen brand preferences, brand loyalty, and prevalence of smoking.
We describe the development and implementation of the Pathways school food service intervention during the feasibility phase of the Pathways study. The purpose of the intervention was to lower the amount of fat in school meals to 30% of energy to promote obesity prevention in third- through fifth-grade students. The Pathways nutrition staff and the food service intervention staff worked together to develop 5 interrelated components to implement the intervention. These components were nutrient guidelines, 8 skill-building behavioral guidelines, hands-on materials, twice yearly trainings, and monthly visits to the kitchens by the Pathways nutrition staff. The components were developed and implemented over 18 mo in a pilot intervention in 4 schools. The results of an initial process evaluation showed that 3 of the 4 schools had implemented 6 of the 8 behavioral guidelines. In an analysis of 5 d of school menus from 3 control schools, the lunch menus averaged from 34% to 40% of energy from fat; when the menus were analyzed by using the food preparation and serving methods in the behavioral guidelines, they averaged 31% of energy from total fat. This unique approach of 5 interrelated food service intervention components was accepted in the schools and is now being implemented in the full-scale phase of the Pathways study in 40 schools for 5 y.
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The importance of the role of an advanced practice nurse in infectious diseases has been heightened by the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic. The unique abilities that are part of the expanded role enable the advanced practice nurse to utilize tools learned as a nurse and combine them with advanced clinical skills to be a comprehensive care provider. The clinical management of the patient with HIV is complex and requires up-to-date knowledge regarding the constantly changing science of the virus.