Biomedical subjects

John Marshall

Publications and source records attributed to John Marshall.

At least 91 records · Page 5Linked to original sources

PubMed2003

Influence of perceived functional and employment status on cardiopulmonary resuscitation directives.

BACKGROUND: Perceptions about functional and employment status before admission to the intensive care unit (ICU) may influence how patients and clinicians make decisions about cardiopulmonary resuscitation. OBJECTIVE: To examine the relationship between cardiopulmonary resuscitation directives established within 24 hours of admission to the ICU and clinical perceptions of premorbid functional and employment status. DESIGN: Prospective observational study in 15 university-affiliated centers in Canada, the United States, Australia, and Sweden. PATIENTS: A total of 1,008 ICU patients aged 18 years or older expected to stay in the ICU at least 72 hours. MEASUREMENTS: By using multinomial logistic regression, we examined the relationship between functional status and employment status perceived by the ICU team 1 month before ICU admission (the independent variables) and resuscitation status (the dependent variable). Each patient had either an explicit resuscitation directive (to resuscitate or not to resuscitate), or an implicit resuscitation directive to resuscitate. RESULTS: On average, patients were 61.7 years (+/-17.4 y) old with an Acute Physiology and Chronic Health Evaluation (APACHE) II score of 21.5 (+/-8.7); 846 (83.9%) were ventilated mechanically within 48 hours and 345 (34.2%) died in the ICU. Most patients (793, 78.7%) had no explicit resuscitation directive; 98 (9.7%) had an explicit plan to resuscitate, whereas 117 (11.6%) had an explicit plan of do-not-resuscitate. Of 1,008 patients, 98 (9.7%) were severely functionally limited, 217 (21.5%) were somewhat limited, 628 (62.3%) were totally independent, and 65 (6.4%) had unknown functional status 1 month before ICU admission. Severe functional status impairment was associated moderately with an explicit plan to resuscitate (odds ratio, 2.2 relative to no explicit directive) and associated strongly with an explicit do-not-resuscitate plan (odds ratio, 6.2 relative to no explicit directive, P value on the difference =.011). This relationship was not influenced by age, sex, APACHE II score, medical or surgical status, admission diagnosis, employment status, or city. However, severe functional status was associated strongly and significantly with an explicit do-not-resuscitate directive among those who could not participate in decision making (odds ratio, 8.2; 95% confidence interval, 4.5-15.0), and more weakly associated in those who could participate (odds ratio, 1.7; 95% confidence interval, 0.3-8.6). Being unemployed was associated with an increased odds of an explicit resuscitation directive versus no explicit directive (odds ratio, 5.5; 95% confidence interval, 2.2-13.4). CONCLUSIONS: Functional status impairment perceived by the ICU team is associated clearly with do-not-resuscitate directives in patients unable to participate in decision making. However, the association appears much weaker in patients able to participate in decision making. PATIENTS' perceived employment status also may influence resuscitation decisions. Our results emphasize the challenges of ensuring that crucial resuscitation decisions are not affected adversely by patients' inability to participate in decisions, and by their functional and employment status.

APACHE↗

PubMed2003

A novel ELISPOT assay to enhance detection of antigen-specific T cells employing antigen-presenting cells expressing vector-driven human B7-1.

The ELISPOT assay is used to detect T-cell responses in patients enrolled in vaccine clinical trials; it is a relatively sensitive assay that can be performed without in vitro stimulation (IVS) of PBMC. However, this assay may be limited in some cases because of a weak signal 1 (as is the case for tumor-associated antigens [TAA]), or by a limited number of PBMC available from patients. The objective of this study is to enhance the sensitivity of the ELISPOT by increasing the level of signal 2, in this case, B7-1 expression on antigen-presenting cells (APC), allowing for a more sensitive detection of antigen-specific T-cell precursors. C1RA2 cells were used as APC and were uninfected, or infected with either recombinant avipox (fowlpox)-B7-1 (rF-B7-1) or control fowlpox wild-type (FP-WT) vector. The expressions of B7-1, MHC Class II, as well as HLA-A2 on the infected cells were analyzed by flow cytometry. A nearly threefold increase in B7-1 mean fluorescence intensity (MFI) occurred in the rF-B7-1-infected C1RA2 cells with no changes in MHC Class II or HLA-A2 expression. Various PBMC/APC ratios were used to further analyze the use of rF-B7-1-infected C1RA2 cells as APC in the ELISPOT assay. Fewer APC were required to activate PBMC when C1RA2 infected with rF-B7-1 were used as APC. Furthermore, using a PBMC/APC ratio of 1:1, similar detection was achieved using fewer PBMC. In addition, we demonstrated that the reactivity can be blocked by adding anti-B7-1 antibody. We performed the assay using APC on five normal healthy donors. All five donors showed substantial increases in PF to the Flu matrix peptide (Flu peptide) using the rF-B7-1-infected C1RA2 cells. Finally, we evaluated five cancer patients who received a carcinoembryonic antigen (CEA) vaccine-based therapy. Increases in CEA peptide precursors were noted in all five patients using the B7-1-infected APC. In conclusion, we have demonstrated the ability to enhance the sensitivity of the ELISPOT assay through infection of C1RA2 with rF-B7-1.

Antigen-Presenting Cells↗

PubMed2003

An unusual case of ovarian resistance syndrome.

BACKGROUND: Women who present with elevated gonadotropins, primary amenorrhea, and sexual infantilism usually have an abnormal karyotype or premature ovarian failure. We describe a rare case of ovarian resistance secondary to a gonadotropin post-receptor defect. CASE: An 18-year-old presented with amenorrhea and sexual infantilism. Original workup led physicians to believe the patient had uterine agenesis with premature ovarian failure. Ovarian biopsy proved the presence of follicles. After 48 months on hormone replacement, the patient went through the stages of puberty, including menarche. Re-evaluation proved the presence of a uterus. CONCLUSION: Ovarian resistance is a rare cause of hypergonadotropic hypogonadism. With this type of ovarian dysfunction, women present early in life with amenorrhea, elevated gonadotropins, and normal karyotypes.

Adult↗

PubMed2003

Carcinoembryonic antigen-based vaccines.

Carcinoembryonic antigen (CEA) is a glycoprotein that is normally expressed in certain parts of the body and commonly overexpressed in most carcinomas of the colon, rectum, breast, lung, pancreas, and gastrointestinal tract. Increased expression of CEA promotes increased intercellular adhesions, which may lead to metastasis. Carcinoembryonic antigen is often used as a serologic marker of malignancy because of its overexpression in cancer as well as its measurability in serum. However, because CEA is normally expressed in the body, the immune system commonly becomes tolerant to it. If this tolerance can be overcome without leading to autoimmune disease, CEA vaccination therapy could be immensely beneficial to cancer patients. A number of preclinical and clinical studies have been conducted on the use of recombinant CEA-vaccinia virus vaccines and recombinant ALVAC-CEA vaccines. In general, the vaccines have been well tolerated and effective at inducing CEA-specific cytotoxic T-cell responses, especially when used in the presence of the T-cell costimulatory molecule B7.1. "Prime and boost" techniques combining both types of vaccines and the addition of cytokines such as granulocyte-macrophage colony-stimulating factor have resulted in enhanced T-cell responses. The combination of vaccinia or ALVAC vaccines with a triad of costimulatory molecules (B7.1, ICAM-1, and LFA-3) has also stimulated significant T-cell increases. This review summarizes these studies and discusses the role of CEA in cancer immunotherapy.

Cancer Vaccines↗

PubMed2003

In vitro model for the study of human posterior capsule opacification.

PURPOSE: To develop and evaluate a model for the organ culture of human lens capsules that reduces problems inherent in preexisting models for the study of in vitro posterior capsule opacification (PCO). METHODS: Human lenses (N = 110) were isolated from donor eyes and supported externally within a lens holder system by medical-grade cyanoacrylate glue, allowing visualization of the entire capsular bag. After capsulorhexis and lens extraction were performed, the capsule specimens were maintained at physiological conditions for up to 4 weeks. The area of lens epithelial cell (LEC) coverage over the posterior capsule surface was determined objectively on a daily basis using a graticule. Lens epithelial cell behavior was correlated with clinical data and other in vitro PCO models. RESULTS: Cyanoacrylate glue did not appear to be toxic to LECs at the concentration used. The amount of viable epithelium after nuclear extraction was dependent on the age and postmortem time of the specimen. Viable LEC cultures were obtained from eyes up to 9 days postmortem. The time from death to culture or from enucleation to culture did not influence LEC viability if it was fewer than 5 days. The LEC proliferation rates and confluence times were age dependent and correlated closely between pairs of eyes. CONCLUSIONS: Results show that the lens holder model is a more physiological method for supporting the capsule and is a robust, reproducible system for the study of LEC migration and proliferation. It allows visualization within the entire capsular bag. Intraocular lenses can be implanted in this system in a way that more closely resembles the in vivo scenario. This model can be used to evaluate therapeutic measures to prevent PCO.

Adolescent↗

PubMed2003

Elliptical ELSA (LASEK) instruments for the treatment of astigmatism.

PURPOSE: To investigate newly designed, elliptical ELSA (excimer laser subepithelial ablation) instruments for the treatment of astigmatism. SETTING: University Eye Clinic Regensburg, Regensburg, Germany, and the Rayne Institute, Department of Ophthalmology, St. Thomas' Hospital, London, United Kingdom. METHODS: The new ELSA instrument set consists of an elliptical microtrephine (11.0 mm x 8.0 mm) with a 70 microm calibrated blade and an elliptical alcohol cone (11.5 mm x 8.5 mm). With this instrument set, ELSA (the laser-assisted subepithelial keratectomy [LASEK] described by Camellin) was performed in 34 astigmatic eyes. The cylindrical correction was between 1.00 diopters (D) and 3.50 D and the spherical correction, between -0.75 D and -8.75 D. In all eyes, the follow-up was 6 months. The postoperative refractive outcome was analyzed using Alpins vector analysis. RESULTS: Excimer laser subepithelial ablation was performed without intraoperative complications in all eyes. At 6 months, the mean spherical correction was -0.04 D +/- 0.27 (SD) (range +0.75 to -0.75 D) and the mean cylindrical correction, 0.27 +/- 0.23 D (range 0 to 0.75 D). The mean index of success was 0.18 +/- 0.15. CONCLUSIONS: With the elliptical instruments, ELSA was an effective and safe surgical procedure for astigmatism.

Astigmatism↗

PubMed2003

Fourier analysis of induced irregular astigmatism. Photorefractive keratectomy versus laser in situ keratomileusis in a bilateral cohort of hyperopic patients.

PURPOSE: To analyze corneal topographic data by Fourier analysis to determine differences in irregular astigmatism following spherical hyperopic correction by photorefractive keratectomy (PRK) or laser in situ keratomileusis (LASIK). SETTING: Department of Ophthalmology, St. Thomas' Hospital, London, United Kingdom. METHODS: Thirty-six eyes of 18 patients with moderate hyperopia had LASIK in 1 eye and PRK in the other eye. The flap was cut on a nasal hinge with a Moria LSK One microkeratome. The laser was a Summit SVS Apex Plus with an optical zone of 6.5 mm and a blending zone of 1.5 mm. Corneal topographic data were acquired with a TMS-1 topographer (Computed Anatomy Inc.) preoperatively and 1, 3, 6, and 12 months postoperatively. The ASCII files containing the dioptric power values were extracted and analyzed with custom-written software to extract the Fourier harmonics. RESULTS: The irregular astigmatism increased in both groups postoperatively, peaking at 3 months and then decreasing over the next 9 months. There was no statistically significant difference between the 2 groups at any time point (P<.05). The change in the topographically derived equivalent sphere showed undercorrection in both groups at all time points. Regular astigmatism showed a marginal statistically significant increase in the LASIK group at 12 months (P =.049). CONCLUSION: Irregular astigmatism, equivalent sphere, and regular astigmatism were not significantly different in the PRK and LASIK groups during the follow-up. Based on the corneal topography, the 2 procedures induced an equal amount of irregular astigmatism.

Adult↗

PubMed2003

Rotavirus detection and characterisation in outbreaks of gastroenteritis in aged-care facilities.

BACKGROUND: Although rotavirus is a major cause of gastroenteritis in children, its role in adult gastroenteritis and the sensitivity of different methods for its detection in specimens collected from adults are less well understood. OBJECTIVES: (1) To examine the frequency and seasonality of rotavirus-associated gastroenteritis outbreaks in aged-care facilities in Victoria, Australia. (2) To determine rotavirus type in these outbreaks. (3) To determine whether other enteropathogenic agents are present in specimens from these outbreaks. (4) To examine the sensitivity of different methods (electron microscopy (EM), reverse transcription-polymerase chain reaction (RT-PCR), enzyme immunoassay (EIA) and latex agglutination (LA)) for the detection of rotavirus in specimens from adults. STUDY DESIGN: Specimens from gastroenteritis outbreaks in aged-care facilities forwarded to this laboratory for the years 1997-2000 were tested for enteropathogenic agents by various methods. Epidemiological, clinical and seasonal data from the rotavirus-positive outbreaks were analysed. RESULTS: Rotavirus was detected by EM in 18 out of 29 individuals associated with seven out of 53 (13%) gastroenteritis outbreaks in aged-care facilities; norovirus was detected in 22 outbreaks (42%) and astrovirus in one outbreak (2%). No mixed viral infection was found in any outbreak. All rotaviruses were typed as Group A by RT-PCR. The rotaviruses in the seven outbreaks were G-typed as follows: G2 (three outbreaks), G4 (two outbreaks), G1 (one outbreak) and G9 (one outbreak). The rotavirus-associated outbreaks were concentrated in mid-winter to mid-spring. The relative sensitivities of the Group A rotavirus detection methods (for the 29 specimens tested) were EM (18), first-round RT-PCR (11), second-round PCR (19), EIA-visual (19), EIA-photometric (19) and LA (13). CONCLUSIONS: In Victoria, Australia, outbreaks of gastroenteritis associated with rotavirus are quite common in aged-care facilities. They involve Group A rotavirus and have a winter/spring seasonality. G-types G1, G2, G4 and G9 were all detected. EIA, second-round PCR and EM proved sensitive methods for rotavirus detection whereas first-round RT-PCR and LA did not.

Aged↗

PubMed2003

Tumor suppressor p16INK4a determines sensitivity of human cells to transformation by cooperating cellular oncogenes.

The Ink4a/Arf locus encodes two distinct proteins, both of which may contribute to senescence and tumor suppression. We find that human diploid fibroblasts (HDFs) that are specifically deficient for p16INK4a achieve anchorage independence when transduced with retroviruses encoding telomerase (hTERT) and either Ras or Myc. Significantly, Ras and Myc together enable the cells to form tumors in nude mice but at a frequency that suggests additional genetic changes. All five tumors analyzed expressed high levels of Ras and retained functional p53, although two showed downregulation of Arf. Cytogenetic analyses identified clonal chromosomal alterations that may have contributed to tumorigenesis, but the tumor cells were essentially diploid.

Animals↗

PubMed2003

The effect of posterior capsule opacification on visual function.

PURPOSE: To investigate how posterior capsule opacification (PCO) affects visual function in pseudophakic eyes. METHODS: One hundred and six eyes that had undergone uncomplicated phacoemulsification were recruited sequentially. Patients with surgical complications or other ocular disease were excluded. PCO was assessed by a digital retroillumination camera using a software program based on the analysis of texture in the image, and the percentage area within the central 3-mm zone of the posterior capsule was calculated. Visual function assessment included Early Treatment Diabetic Retinopathy Study (ETDRS) high- and low-contrast visual acuity, contrast sensitivity with the Pelli-Robson and CSV-1000 grating charts, and forward light-scatter by the direct-compensation method (van den Berg). RESULTS: The percentage PCO required for decline in high-contrast ETDRS was 78%; for low-contrast acuity and Pelli-Robson, 46%; for CSV-1000 contrast sensitivity, 38% to 51%; and for forward light-scatter, less than 1% PCO. CONCLUSIONS: Central PCO affects psychophysical test results with differing degrees of sensitivity. Forward light-scatter is the most sensitive, followed by contrast sensitivity and visual acuity.

Aged↗

PubMed2003

Human retinal molecular weight exclusion limit and estimate of species variation.

PURPOSE: To determine the maximum size of molecule capable of freely diffusing across human retina, referred to as the retinal exclusion limit (REL), and the location of any sites of high resistance to diffusion. To assess the degree of interspecies variation in the REL of three animals commonly used to model human disease. METHODS: Trephines of human neuroretina were mounted in a modified Ussing chamber. FITC-dextrans of various molecular weights (MWT) were dissolved in phosphate-buffered saline, and the rate of transretinal diffusion was determined over 24 hours with a spectrophotometer. The theoretical REL was calculated by extrapolating the linear relationship between the rate of diffusion and log(MWT). In separate experiments to determine the sites of barrier to diffusion, FITC-dextrans with a MWT greater than the calculated REL were applied to either the inner or outer retinal surface, processed as frozen sections, and viewed with a fluorescence microscope. Experiments to determine the REL were repeated in bovine, porcine, and rabbit retina. RESULTS: The REL in human tissue was 76.5+/-1.5 kDa (6.11+/-0.04 nm). The inner and outer plexiform layers formed the sites of highest resistance to diffusion. The REL in pigs, cattle, and rabbits were 60 +/- 11.5, 78.5 +/- 20.5, and 86 +/- 30 kDa, respectively (5.68 +/- 0.45, 6.18 +/- 0.61, and 6.38 +/- 0.88 nm). CONCLUSIONS: In humans, the inner and outer plexiform layers are sites of high resistance to the diffusion of large molecules, resulting in an REL of 76.5 kDa. There was only moderate interspecies variation in the REL of the animals studied, suggesting that they provide adequate models for the study of human transretinal macromolecular diffusion.

Aged↗

PubMed2003

An experimental model of rhegmatogenous retinal detachment: surgical results and glial cell response.

PURPOSE: To modify existing experimental models to simulate the typical clinical presentation of human rhegmatogenous retinal detachment (RRD), namely an RD caused by a retinal break, in a phakic eye, with a posterior vitreous detachment (PVD); to model RRD in a species that is anatomically similar to humans; and to characterize the glial cell response to RRD. METHODS: Mixed-breed pigs underwent vitrectomy, PVD, subretinal injection of viscoelastic, and creation of a break at the apex of the RD. The crystalline lens was not removed. Follow-up was for 0, 1, and 7 days. Tissue was processed for light and electron microscopy. The glial cell response was characterized using antibodies to glial fibrillary acidic protein (GFAP). RESULTS: Of 11 RRDs created in seven pigs, 10 increased in size and 1 decreased. Light and electron microscopy demonstrated typical features of RD. There was constitutive expression of GFAP in astrocytes and Müller cells with increased immunoreactivity from day 1. CONCLUSIONS: This study provided a model of RRD that simulates the typical clinical presentation in humans. It used techniques that most vitreoretinal surgeons are familiar with, and an animal that is widely available and anatomically similar to humans. Anatomic success was high, and the glial cell response established comparability with other species.

Animals↗

PubMed2002

Differential expression of carcinoembryonic antigen (CEA) splice variants in whole blood of colon cancer patients and healthy volunteers: implication for the detection of circulating colon cancer cells.

Quantification of circulating cancer cells in whole blood samples by real time quantitative RT-PCR might be of clinical value for monitoring therapeutic effectiveness. In colon cancer patients, carcinoembrynic antigen (CEA) and cytokeratin 20 (CK20) have been frequently used for RT-PCR based tumor cell detection, but the specificity in particular for CEA has been questioned. In this study, we compared real-time RT-PCR for CEA and CK20 and analysed patients with metastatic disease (n=32) and healthy volunteers (n=17). CK20 mean values were elevated in cancer patients (P<0.001) and defined a subgroup (38%) who showed CK20 levels at least 100-fold above the highest value of the healthy control group. In contrast, only two cancer patients (6%) showed elevated CEA levels. Samples of the healthy control group showed exclusively a CEA-PCR product of 79 degrees C melting temperature. Thirty per cent of the colon cancer patients showed an additional product of 82 degrees C melting temperature. The 82 degrees C product was identical with the amplification product of CEA-cDNA and cDNA from different colon cancer cell lines. Colon cancer cells were spiked into normal blood in 10-fold dilutions that resulted in a dose dependent shift of the melt curve from 79 degrees C to the 82 degrees C. Sequencing of the PCR products showed that white blood cells express a splice variant of CEA, which hinders detection of tumor cell cDNA in whole blood samples. Our findings have implications for the use of CEA as a diagnostic molecule (e.g. by RT-PCR). The discovery of a physiologically expressed CEA splice variant might lead to a better understanding of the biological function of CEA and its family members.

Adenocarcinoma↗

PubMed2002

Demonstration of feasibility of in vivo gene therapy for Gaucher disease using a chemically induced mouse model.

Progress towards developing gene therapy for Gaucher disease has been hindered by the lack of an animal model. Here we describe a mouse model of Gaucher disease which has a chemically induced deficiency of glucocerebrosidase and that accumulates elevated levels of glucosylceramide (GL-1) in the lysosomes of Kupffer cells. Administration of mannose-terminated glucocerebrosidase (Cerezyme) resulted in the reduction of GL-1 levels in the livers of these animals. Gene transduction of hepatocytes with a plasmid DNA vector encoding human glucocerebrosidase (pGZB-GC) generated high-level expression and secretion of the enzyme into systemic circulation with consequent normalization of Kupffer cell GL-1 levels. This suggested that the de novo synthesized and unmodified enzyme produced by hepatocyte transduction was also capable of being delivered to the cells that are primarily affected in Gaucher disease. Immunolocalization studies also revealed that preferential transduction and expression of human glucocerebrosidase in the Kupffer cells with subsequent reduction in the GL-1 levels could be attained with a low dose of a recombinant adenoviral vector encoding the human enzyme (Ad2/CMV-GC). This observation raises the possibility of gene therapy for Gaucher disease that involves directly transducing the affected histiocytes using recombinant adenoviral vectors. Together, these data demonstrate the potential for use of in vivo gene therapy vectors for treating Gaucher disease.

Adenoviridae↗

PubMed2002

Failure of a discontinuous bend to prevent lens epithelial cell migration in vitro.

PURPOSE: To assess the effect of substrate geometry (discontinuous bend) on lens epithelial cell (LEC) growth in vitro. SETTING: Department of Ophthalmology, St. Thomas' Hospital, London, United Kingdom. METHODS: Culture wells with central depths of 0.4 mm, 1.0 mm, or 3.0 mm and a sharp square-edged profile (discontinuous bend) or a round-edged profile (continuous bend) were produced from a block of poly(methyl methacrylate). Freshly harvested bovine LECs were attached to the center of each well and cultured using standard techniques. Observations were made of whether LECs grew out of the wells and of the time required to do so. RESULTS: Lens epithelial cells migrated out of all the wells. There was no significant difference in the rate at which they migrated out of round-edged and square-edged wells. CONCLUSIONS: In vitro, a sharp discontinuous bend did not appear to induce contact inhibition of migrating LECs nor did it significantly hinder the rate at which LECs migrated. Therefore, a discontinuous bend in the lens capsule in isolation is unlikely to be responsible for the observed reduction in posterior capsule opacification associated with the use of square-edged IOLs.

Animals↗

PubMed2002

Vitality of epithelial cells after alcohol exposure during laser-assisted subepithelial keratectomy flap preparation.

PURPOSE: To evaluate the vitality of epithelial cells after various exposure times to 20% ethanol and epithelial flap preparation in laser-assisted subepithelial keratectomy (LASEK) using the trypan blue dye test. SETTING: University Eye Clinic Regensburg, Regensburg, Germany, and the Rayne Institute, Department of Ophthalmology, St. Thomas' Hospital, London, United Kingdom. METHODS: Five human cadaver eyes were exposed to 20% ethanol for 15, 30, 45, 60, and 120 seconds, respectively. After an epithelial flap (as in LASEK) was prepared, the flap was deliberately cut off. The flaps were soaked in a trypan blue 0.1% solution at 37 degrees C. After 3 washes with phosphate-buffered saline (PBS), the specimens were reincubated for 30 minutes in culture medium containing 10% fetal calf serum at 37 degrees C. After an additional wash with PBS, the cells were observed with a standard inverted light microscope. RESULTS: After 15- and 30-second exposure to 20% ethanol, most epithelial cells were vital. This changed substantially after 45 seconds, when vital and dead cells were approximately equal. Longer exposure times (60 seconds and 120 seconds) showed predominantly dead epithelial cells. CONCLUSIONS: Exposure to 20% ethanol should be 20 to 30 seconds as the number of vital epithelial cells rapidly decreased after that. Vitality of the epithelial flap is probably a crucial factor in the dampened wound response in LASEK compared to that in photorefractive keratectomy.

Cell Survival↗

PubMed2002

Phase II trial of docetaxel chemotherapy in patients with incurable adenocarcinoma of the esophagus.

BACKGROUND: Chemotherapy remains the primary mode of treatment for metastatic carcinoma of the esophagus. The efficacy of various chemotherapeutic regimens has been studied predominantly in patients with squamous cell carcinoma of the esophagus. In light of the increasing incidence of adenocarcinoma of the esophagus, studies evaluating newer chemotherapy agents, such as docetaxel, in this patient population are necessary. The objective of this trial was to determine the complete and partial response rate of docetaxel in patients with incurable adenocarcinoma of the esophagus. PATIENTS AND METHODS: Eligible patients had histologically confirmed metastatic adenocarcinoma of the esophagus or locally extensive disease not curable with surgery or radiation therapy. Patients were either chemotherapy naive or previously treated with chemotherapy (including paclitaxel). Docetaxel was administered at a dose of 75 mg/m2 every three weeks intravenously. Appropriate imaging studies/examinations were obtained after every two cycles to evaluate response. RESULTS: A total of 22 patients were enrolled in the trial. Chemotherapy-naive patients achieved a response rate of 18% (95% CI = 2.3 to 51.8) while patients who received prior chemotherapy achieved a 0% response rate (95% CI = 0 to 25). There were no complete responses. The overall median survival time is 3.4 months and the one-year survival rate is 21%. The toxicities included febrile neutropenia (32%) as well as grade 3 and 4 fatigue (14%) and anorexia (9%). CONCLUSIONS: Although chemotherapy naive patients achieved an 18% response rate and no responses were seen in previously treated patients, the limitations of this trial does not allow for any definitive conclusions to be made about the efficacy of single agent docetaxel chemotherapy in patients with incurable esophageal cancer.

Adenocarcinoma↗

PubMed2002

Growth factors in corneal wound healing following refractive surgery: A review.

The first part of this review article aims to provide important basic definitions of growth factor terminology, and to put forward a model for understanding the role of growth factors in a wound healing context. In the second part of the paper, we review the literature on growth factors in the cornea, including that on changes associated with wound healing following refractive surgery in the epithelial, stromal, and endothelial layers. The role of growth factors in stromal removal, corneal neovascularization, corneal innervation and wound healing is considered. The importance of the epithelial-stromal interaction is discussed, including the role of growth factors in keratocyte apoptosis. In the final section, we review the current literature on endogenous and exogenous modulation of growth factors in corneal wound healing. This includes important in vitro work but aims to emphasize clinically relevant results. Photorefractive keratectomy (PRK) may have short-term complications such as pain and haze, whereas laser in situ keratomilieusis (LASIK) may have longer-term adverse effects on corneal biomechanics. The emerging technique of laser epithelial keratomilieusis (LASEK) provides an interesting alternative wound which may be less susceptible to the inherent complications of PRK and LASIK. At present, the phenomenon of iatrogenic keratectasia following LASIK is not fully understood, but these features of wound healing following PRK may be amenable to growth factor modulation.

Animals↗