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Biomedical subjects

L Ramsey

Publications and source records attributed to L Ramsey.

17 recordsLinked to original sources

Preferential repair by squamous epithelium of thermal induced injury to the proximal stomach in patients undergoing ablation of Barrett's esophagus.

BACKGROUND: The presence of extensions of squamous epithelium into the proximal stomach in patients undergoing routine upper endoscopy has recently been described. The factors that may favor development of squamous epithelium within the proximal stomach remain unknown. METHODS: Patients with Barrett's esophagus who agreed to undergo ablation of Barrett's epithelium by using multipolar electrocoagulation were included. Patients were treated with a high dose of a proton pump inhibitor. The columnar-appearing mucosa was systematically treated. Occasionally, thermal injury was inadvertently induced in the proximal stomach. On endoscopy performed 4 to 6 weeks after treatment, the presence of squamous epithelium extending into the proximal stomach was documented. The use of Lugol's stain assisted in confirming the squamous nature of the abnormal tissue, which was confirmed histologically by cytokeratin immunohistochemistry. RESULTS: The 12 patients included in the study had a mean length of Barrett's epithelium of 3.8 +/- 0.7 cm. Patients were treated with omeprazole, mean dose 66 +/- 6.0 mg, and had a mean percent total time that the pH was less than 4 of 1.9 +/- 0.8. The mean length and width of gastric squamous extensions were 1.7 +/- 0.2 cm and 0.8 +/- 0.1 cm, respectively. None of the squamous extensions into the stomach were documented before mucosal ablation. The extensions stained positively for cytokeratin 13 and negatively for cytokeratin 8, thereby confirming their squamous nature. CONCLUSIONS: Thermal injury to the proximal stomach in patients undergoing ablation of Barrett's epithelium and profound acid suppression results in repair by squamous epithelium. Recognition of this lesion is essential because it may lead to confusion as to the location of the esophagogastric junction in subsequent endoscopic evaluations.

Adult↗

Plasma leptin concentrations in obese children: changes during 4-mo periods with and without physical training.

BACKGROUND: Little is known about the effects of physical training on plasma leptin concentrations in children. OBJECTIVE: We sought to determine the effects of 4-mo periods with and without physical training on leptin in obese children and to explore the determinants of leptin at baseline and in response to physical training. DESIGN: Participants were 34 obese 7-11-y-old children randomly assigned to engage in physical training during either the first or second 4 mo of the 8-mo study. RESULTS: Total body composition, visceral adiposity, and insulin were all positively correlated with leptin at baseline (P < or = 0.05); however, only fat mass was retained in the final stepwise regression (P = 0.0001, R2 = 0.57). Leptin decreased during the 4-mo periods of physical training and increased in the 4 mo after cessation of physical training (P < 0.001 for the time by group interaction). Decreases in leptin were greatest in children with higher pretraining leptin concentrations, those whose total mass increased least, and those whose insulin concentrations decreased most (P < or = 0.05); only pretraining leptin concentration (P = 0.009) and change in total mass (P = 0.0002) were retained in the final regression (R2 = 0.53). CONCLUSIONS: In obese children, leptin concentration decreased during 4 mo of physical training and increased during a subsequent 4-mo period without physical training, fat mass was highly correlated with baseline leptin, and greater reductions in leptin during 4 mo of physical training were seen in children with higher pretraining leptin and in those whose total mass increased least.

Absorptiometry, Photon↗

Biomarker studies in reversed Barrett's esophagus.

OBJECTIVE: The purpose of this study was to use biomarkers to assess for cancer risk in Barrett's esophagus patients with either squamous islands or complete reversal of their intestinal metaplasia to squamous epithelium. METHODS: The biomarkers included proliferation characteristic using Ki-67, p53 abnormalities using immunohistochemical methods with two antibodies, DO-1 and DO-7, and ornithine decarboxylase (ODC) activity. RESULTS: Eleven patients had complete reversal produced by a combination of acid suppression and thermal injury (multipolar electrocoagulation). Ki-67 staining was indistinguishable from that of normal squamous esophageal epithelium, i.e., basal layer staining only. All 11 cases were negative for p53. ODC activity was low and in the range for normal squamous epithelium. Fourteen patients had squamous islands (partial reversal) after prolonged proton pump inhibitor therapy. Multilayer Ki-67 staining occurred in nine cases (64%), and six (43%) had areas of positive p53 staining. CONCLUSIONS: Initial biomarker studies suggest that completely reversed squamous epithelium is biologically similar to normal squamous epithelium and of low cancer risk. In contrast, partial reversal, manifest as squamous islands, is accompanied by biomarker abnormalities.

Aged↗

Effects of ingesting supplements designed to promote lean tissue accretion on body composition during resistance training.

This study examined the effects of ingesting nutritional supplements designed to promote lean tissue accretion on body composition alterations during resistance training. Twenty-eight resistance-trained males blindly supplemented their diets with maltodextrin (M), Gainers Fuel 1000 (GF), or Phosphagain (P). No significant differences were observed in absolute or relative total body water among groups. Energy intake and body weight significantly increased in all groups combined throughout the study with no group or interaction differences observed. Dual energy x-ray absorptiometry-determined body mass significantly increased in each group throughout the study with significantly greater gains observed in the GF and P groups. Lean tissue mass (excluding bone) gain was significantly greater in the P group, while fat mass and percent body fat were significantly increased in the GF group. Results indicate that total body weight significantly increased in each group and that P supplementation resulted in significantly greater gains in lean tissue mass during resistance training.

Absorptiometry, Photon↗

Reproducibility of the measurement of colonic proliferation using bromodeoxyuridine across laboratories.

Although measures of colonic cell proliferation are being used as potential intermediate markers in chemoprevention studies, measurement standardization is still ongoing. This study was designed to assess the reproducibility of the labeling index quantification, as measured by bromodeoxyuridine, across four laboratories experienced in its use. Each institution submitted 10 slides, with one circled area of each slide to be scored. Each site followed its standard procedures for scoring colonic crypts; no attempts to standardize these procedures were made. There was high concordance among the laboratories on whether scorable crypts were present on a particular slide, but only two pairs of laboratories demonstrated agreement statistically greater than that predicted by chance. The overall difference among the sites on the number of scorable crypts was marginally significant (P = 0.083), and there was a highly significant overall difference in the magnitude of the labeling index (P < 0.0001). Sites 1 and 2 tended to have similar results, as did sites 3 and 4, most likely due to common training. Even with these discrepancies, high correlation (r > 0.75) was observed among the reported labeling index values for each pair of laboratories. Without standardized training, these laboratories may differ in the crypts considered appropriate for counting and in whether cells are counted as labeled or unlabeled. These results suggest that standardized training in scoring across all sites performing labeling index determinations is required to assure reproducibility across sites or studies. These results may also help explain discrepancies in the average values of the labeling index reported in the literature.

Analysis of Variance↗

Demonstration of a field defect in gastric intestinal metaplasia by biological marker analysis.

Gastric intestinal metaplasia (GIM) is a precursor lesion for gastric cancer. It most frequently involves the antrum and the angularis. At endoscopy, it is not possible to visually distinguish GIM from normal stomach. Furthermore, GIM frequently has a patchy distribution with areas of metaplasia coexisting with adjacent areas of other histologies, including normal stomach. In this study we sought to determine whether a "field defect" could be demonstrated in subjects with GIM, involving the entire region of the stomach. The biologic markers tested were ornithine decarboxylase (ODC) activity and bromodeoxyuridine labeling index (LI). Antral biopsies were obtained from 13 subjects with known GIM and 9 controls (no GIM based on multiple biopsies and absence of methylene blue staining). Three adjacent biopsies were obtained for ODC, LI, and histology. Group I consisted of a set of 3 biopsies from the 9 controls. In the 13 subjects with GIM, 2 sets of 3 biopsies were taken with methylene blue guidance in an attempt to obtain both GIM-free (group II) and GIM-containing (group III) tissue. ODC activities were markedly and statistically significantly (P = 0.0001) elevated in groups II and III versus group I; the mean +/- SDs were 0.075 +/- 0.117 for group I, 1.20 +/- 0.83 for group II, and 1.14 +/- 0.76 for group III. Group II versus Group III values were not different (P = 0.979). LI was less discriminatory with more overlap between the groups. The highest LI was in group II, which was significantly different from group I (P = 0.014) and group III (P = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Clinical experience with the micronucleus assay.

Because of the logistical and practical problems that make cancer prevention trials using cancer incidence as an endpoint virtually impossible to conduct for the majority of cancer types, there is a desperate need for valid intermediate markers of cancer risk to serve as surrogate endpoints in chemoprevention trials. A long and continually growing list of potential markers has been developed in the recent past. Unfortunately very few, if any, of them have been subjected to the usual quality control requirements for a laboratory test before being applied to clinical settings. Modulation of micronuclei frequency has been reported in a number of chemoprevention trials involving the oral cavity, esophagus, lung, and lower GI tract; however, we have focused our efforts primarily on applying the assay to exfoliated buccal mucosal cells, since much of the published data deal with this site, and oral cancer prevention is the theme of one of our chemoprevention trials. After standardizing the definition of a micronucleus by literature review and direct exchange of slides and photographs with other investigators active in the field, we obtained smears from normal subjects, smokers with or without leukoplakia, and tobacco chewers with or without leukoplakia. Our summarized findings follow: (1) Micronuclei represent only one of numerous cytological abnormalities in exfoliated buccal cells that are manifest particularly in tobacco chewers. These include a high frequency of anucleate, binucleate, and multinucleated cells, abnormal shapes and sizes of nuclei, etc.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticarcinogenic Agents↗

Oral cancer prevention: the case for carotenoids and anti-oxidant nutrients.

The most convincing evidence for a preventive role for any modality is obviously demonstration of incidence reduction produced by that modality. However, cancer prevention trials with cancer incidence as an endpoint have logistic problems rendering them essentially impossible to conduct for most malignancies. Hence a workable strategy often involves analysis of other, indirect lines of evidence to reach conclusions. For oral cancer, dietary epidemiologic evidence points to a protective role for foods rich in carotenoids. Other anti-oxidants, such as vitamin C, are also implicated. Similarly, laboratory evidence points to a carcinogenesis inhibitory role for both retinoids and carotenoids. Clinical studies have targeted premalignant lesions, i.e., oral leukoplakia. For over two decades the efficacy of retinoids, natural and synthetic, has been known. Nevertheless, it has been difficult to translate this into a recommendation for prevention because of the toxicity of retinoids. The synthetic retinoid most often used in these trials is 13-cis-retinoic acid. This compound is toxic even at very low doses (0.1 mg/kg/day), particularly when given over several weeks to months. Hence, although effective, it cannot be advocated for prevention or oral cavity cancer. Studies with nontoxic antioxidants, such as beta-carotene, are much more recent. Early results are promising in that beta-carotene, alone or in combination with other nutrients, can reverse oral leukoplakia without toxicity in short-term trials. Studies currently under way will demonstrate whether durable remissions can be obtained using this strategy. It should be emphasized that such long-term trials are problematic to conduct with the toxic retinoids because the risks of prolonged exposure to them outweighs the chance of cancer development in the usual leukoplakia lesion.

Animals↗

Fragile X syndrome--a review.

Since the discovery of the Fragile X syndrome some 20 years ago, there have been numerous articles concerning clinical features, cognitive profile and transmission. It is a syndrome of importance to all those working in the mental health field and those involved in community health, such as General Practitioners, since it is second only to Down syndrome as a genetic cause of mental handicap.

Abnormalities, Multiple↗

Tissue culture of epithelial cells from esophageal specialized columnar epithelium (Barrett's esophagus).

A procedure is described for the tissue culture of epithelial cells from Barrett's specialized columnar epithelium. The method employs use of nonenzymatic disaggregation techniques and use of a specialized growth medium, M-19. Successful growth can be achieved in 60-70% of cases. Characteristics of four cultures are presented including PAS, Alcian blue, and cytokeratin staining properties. Ultrastructural studies showed the presence of distended rough endoplasmic reticulum, abundant Golgi apparatus, glycogen granules, and cell-cell junctional complexes. Colony formation in anchorage-independent growth in soft agar was not observed in any culture. The cultured cells were not capable of indefinite growth. Thus, they do not behave as fully transformed cells. Availability of this culture system should be of use to the study of the biology of this metaplastic premalignant lesion.

Barrett Esophagus↗

Ki-67 labeling index is a more reliable measure of solid tumor proliferative activity than tritiated thymidine labeling.

The proliferative activity of tumors has been shown to have prognostic significance in a variety of solid tumors. The standard method for assessing the proliferating fraction has been the measurement of the tritiated thymidine labeling index (TLI). Ki-67 is a monoclonal antibody that labels proliferating cells. In this study, the authors compared the proliferative activity of seven solid tumor specimens, using both methods simultaneously, on comparable sections from the same specimen. As expected, in every case the Ki-67 labeling index (KiLI) was greater than the TLI. The mean TLI ranged from 4.4 +/- 0.4% to 16.7 +/- 10.2%. The KiLI from these same tumors ranged from 25.7 +/- 8.6% to 41.2 +/- 12.2%. The mean coefficient of variation for measurements from different sections within the same specimen was 28.8 for TLI and 16.4 for KiLI. Therefore, KiLI shows less variability within different sections of the same specimen and is, therefore, a more reliable marker for proliferative activity than is TLI.

Antibodies, Monoclonal↗

Long-term histologic study of a new carbon-carbon ossicular replacement prosthesis.

In a variety of structural forms, carbon possesses certain properties that render it suitable for implantation in the human body. This report analyzes biocompatibility of a new carbon-carbon prosthesis following long-term middle ear implantation in a prospective, controlled animal study. The prosthesis was placed in the left ear of 20 healthy guinea pigs and in the dorsal subcutaneous tissues for control. The right ear also served as control. Preoperative and postoperative auditory evoked potentials were recorded and compared. Samples of tissue from all three sites were evaluated at 3 and 6 months by light microscopy. The implants also were evaluated by scanning electron microscopy. Samples of lymph nodes, liver, spleen, and lungs also were examined. Fourteen animals (70%) demonstrated no change in auditory evoked potentials postoperatively. One animal developed unilateral dysfunction and three others developed bilateral dysfunction for unexplained reasons. No significant tissue destruction or inflammation of the tissues and no digestion or erosion of the implants were observed. No passage of carbon particles into the reticuloendothelial system was identified. These preliminary results suggest that this new carbon-carbon prosthesis may be biocompatible at 6 months follow-up in the guinea pig and encourage further investigation.

Animals↗