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Biomedical subjects

W Oliver

Publications and source records attributed to W Oliver.

At least 19 recordsLinked to original sources
PubMed2004

Is 'virtual histology' the next step after the 'virtual autopsy'? Magnetic resonance microscopy in forensic medicine.

AIM: The study aimed to validate magnetic resonance microscopy (MRM) studies of forensic tissue specimens (skin samples with electric injury patterns) against the results from routine histology. METHODS AND RESULTS: Computed tomography and magnetic resonance imaging are fast becoming important tools in clinical and forensic pathology. This study is the first forensic application of MRM to the analysis of electric injury patterns in human skin. Three-dimensional high-resolution MRM images of fixed skin specimens provided a complete 3D view of the damaged tissues at the site of an electric injury as well as in neighboring tissues, consistent with histologic findings. The image intensity of the dermal layer in T2-weighted MRM images was reduced in the central zone due to carbonization or coagulation necrosis and increased in the intermediate zone because of dermal edema. A subjacent blood vessel with an intravascular occlusion supports the hypothesis that current traveled through the vascular system before arcing to ground. CONCLUSION: High-resolution imaging offers a noninvasive alternative to conventional histology in forensic wound analysis and can be used to perform 3D virtual histology.

Adult↗
PubMed2001

A case-control study of gastric cancer in Venezuela.

A case-control study to evaluate risk factors for gastric cancer was carried out among 292 cases of gastric cancer and 485 controls in a high-risk area of Venezuela. Subjects were interviewed using a structured questionnaire, which elicited information on residential history, socio-economic status, family history of gastric diseases, smoking, drinking and dietary habits. Habitual diet was estimated from a meal-structured food frequency questionnaire on 75 food items. There was a strong inverse association with social class, as measured by education and by indicators of poverty. The results of the dietary analysis suggest that a diet high in starch and low in meat, fish and fresh vegetables increases risk of gastric cancer. A protective effect was observed for frequent consumption of allium vegetables. Inverse associations were found with height, which may reflect nutritional status in childhood, and with refrigerator use in the first two decades of life. Alcohol and tobacco consumption was investigated among males only, since the prevalence of alcohol and tobacco use was very low in females. Alcohol drinkers were at higher risk than non-drinkers and there was a small excess risk for current smokers compared with never smokers. There was some evidence of familial aggregation of gastric cancer. These findings will have important implications in planning preventive strategies for gastric cancer in Venezuela.

Adult↗
PubMed2000

Lewis antigen alterations in a population at high risk of stomach cancer.

Anomalous Lewis(a) antigen and sulfomucin expression are considered as markers of progression in precursor lesions of gastric cancer. Additionally, Lewis antigen and secretor phenotype have been related to Helicobacter pylori infection and gastric epithelial damage. The two objectives of this study were to correlate Lewis antigen alterations with histochemical changes and to explore the relationship between Lewis and secretor phenotypes and gastric epithelial damage related to H. pylori infection. The study subjects were selected from a chemoprevention trial in Tachira State, Venezuela, an area with a high risk of gastric cancer. Anomalous Lewis(a) antigen expression in Lewis (a-b+) phenotype individuals was closely related to the severity of the histological lesions, especially to dysplasia and type III intestinal metaplasia lesions. A weak relationship was observed between nonsecretor individuals and more advanced lesions of IM, but this association was not statistically significant. There was no relationship between secretor phenotype and H. pylori status, atrophy, regenerative activity, erosion, or ulcer.

Adult↗
PubMed2000

Helicobacter pylori and stomach cancer: a case-control study in Venezuela.

The role of Helicobacter pylori infection in gastric cancer was evaluated in a high-risk population in Venezuela using serological assays in a study of 302 cases and 483 neighborhood controls. To investigate the claim that assays for H. pylori should use antigens derived from local strains, four different assays derived from Venezuelan and European strains were used. Prevalence of IgG H. pylori antibodies in controls was very high, with estimates between 72 and 92%. Prevalence was similar in cases and controls. However, cases had lower antibody titers. This effect was observed only in subjects with low pepsinogen (PG) levels PGI/PGII <3.0), which suggested that extensive atrophy in cases causes a loss of H. pylori infection, with a consequent reduction in antibody titer. In addition, advanced cases (stage II or higher) had lower antibody titers than less advanced cases, which indicated that the lower antibody titers in cases may be attributable partially to a diminished immune response. All of the four assays for anti-H. pylori antibodies gave similar results. No evidence was found for the superiority of the assay based on Venezuelan strains. These results are consistent with other case-control studies in high-risk populations and highlight the difficulties of investigating H. pylori infection in retrospective studies.

Adult↗
PubMed1998

N-(2-Benzoylphenyl)-L-tyrosine PPARgamma agonists. 1. Discovery of a novel series of potent antihyperglycemic and antihyperlipidemic agents.

We have identified a novel series of antidiabetic N-(2-benzoylphenyl)-L-tyrosine derivatives which are potent, selective PPARgamma agonists. Through the use of in vitro PPARgamma binding and functional assays (2S)-3-(4-(benzyloxy)phenyl)-2-((1-methyl-3-oxo-3-phenylpropenyl)+ ++amin o)propionic acid (2) was identified as a structurally novel PPARgamma agonist. Structure-activity relationships identified the 2-aminobenzophenone moiety as a suitable isostere for the chemically labile enaminone moiety in compound 2, affording 2-((2-benzoylphenyl)amino)-3-(4-(benzyloxy)phenyl)propionic acid (9). Replacement of the benzyl group in 9 with substituents known to confer in vivo potency in the thiazolidinedione (TZD) class of antidiabetic agents provided a dramatic increase in the in vitro functional potency and affinity at PPARgamma, affording a series of potent and selective PPARgamma agonists exemplified by (2S)-((2-benzoylphenyl)amino)-3-¿4-[2-(methylpyridin-2-ylamino+ ++)ethoxy ]phenyl¿propionic acid (18), 3-¿4-[2-(benzoxazol-2-ylmethylamino)ethoxy]phenyl¿-(2S)-((2- benzoylph enyl)amino)propanoic acid (19), and (2S)-((2-benzoylphenyl)amino)-3-¿4-[2-(5-methyl-2-phenyloxazol-4-y l)e thoxy]phenyl¿propanoic acid (20). Compounds 18 and 20 show potent antihyperglycemic and antihyperlipidemic activity when given orally in two rodent models of type 2 diabetes. In addition, these analogues are readily prepared in chiral nonracemic fashion from L-tyrosine and do not show a propensity to undergo racemization in vitro. The increased potency of these PPARgamma agonists relative to troglitazone may translate into superior clinical efficacy for the treatment of type 2 diabetes.

Administration, Oral↗
PubMed1998

N-(2-Benzoylphenyl)-L-tyrosine PPARgamma agonists. 3. Structure-activity relationship and optimization of the N-aryl substituent.

3-¿4-[2-(Benzoxazol-2-ylmethylamino)ethoxy]phenyl¿-(2S)-((2- benzoylph enyl)amino)propionic acid (1) and (2S)-((2-benzoylphenyl)amino)-3-¿4-[2-(5-methyl-2-phenyloxazol-4-y l)e thoxy]phenyl¿propionic acid (2) are peroxisome proliferator-activated receptor gamma (PPARgamma) agonists and have antidiabetic activity in rodent models of type 2 diabetes. As part of an effort to develop the SAR of the N-2-benzoylphenyl moiety of 1 and 2, a series of novel carboxylic acid analogues, 23-66, modified only in the N-2-benzoylphenyl moiety were synthesized from L-tyrosine and evaluated as PPARgamma agonists. In general, only modest changes in the N-2-benzoylphenyl moiety of 1 and 2 are tolerated. More specifically, the best changes involve bioisosteric replacement of one of the two phenyl rings of this moiety. Addition of substituents to this moiety generally produced compounds that are less active in the cell-based functional assays of PPARgamma activity although binding affinity to PPARgamma may be maintained. A particularly promising set of analogues is the anthranilic acid esters 63-66 in which the phenyl ring in the 2-benzoyl group of 1 and 2 has been replaced by an alkoxy group. In particular, (S)-2-(1-carboxy-2-¿4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phen yl¿ ethylamino)benzoic acid methyl ester (63) has a pKi of 8.43 in the binding assay using human PPARgamma ligand binding domain and a pEC50 of 9.21 in the in vitro murine lipogenesis functional assay of PPARgamma activity. Finally, 63 was found to normalize glycemia when dosed at 3 mg/kg bid po in the Zucker diabetic fatty rat model of type 2 diabetes.

Administration, Oral↗
PubMed1997

Histological diagnosis of precancerous lesions of the stomach: a reliability study.

BACKGROUND: Within the framework of a chemoprevention trial on stomach cancer, two substudies based on repeat measurement were undertaken to evaluate reliability of histological diagnoses of gastric precancerous lesions. METHODS: A subgroup of 45 subjects received two endoscopies separated by a period of one month. The two biopsies were reviewed by a single pathologist. A second subsample of 50 subjects had a single endoscopy and the biopsy results were reviewed by two pathologists. Agreement between the two diagnoses was assessed by Cohen's Kappa and by repeat frequency. RESULTS: When the same samples were reviewed by the pathologists involved in the trial, agreement was very high for advanced lesions (repeat frequency = 0.96 for intestinal metaplasia and 1.00 for dysplasia) but lower for less advanced lesions (repeat frequency = 0.73 for superficial gastritis and chronic gastritis, 0.65 for atrophic gastritis). When the same pathologist reviewed two sets of biopsies taken less than 2 months apart, the combination of random observer error and biopsy sampling error gave rise to quite low agreement, especially for early lesions, mainly attributable to biopsy sampling error. Comparison of diagnoses made at routine reading and at review by the same pathologist and by different pathologists showed substantial overall agreement with the exception of one pathologist for whom agreement was moderate. CONCLUSIONS: These results confirm that misclassification of histological diagnosis may be a relevant problem in chemoprevention trials of stomach cancer, more so when baseline diagnosis is taken into account in the analysis to estimate progression and regression rates of precancerous lesions. Further, the results suggest that misclassification is limited to early lesions, while diagnostic reliability of severe lesions is quite high.

Adult↗
PubMed1996

Determinants of plasma anti-oxidant vitamin levels in a population at high risk for stomach cancer.

Our objective was to identify the determinants of plasma levels of anti-oxidant vitamins which have been linked with decreased risk of cancer and other chronic diseases. Correlation analyses were performed between baseline plasma levels of ascorbic acid, alpha- and beta-carotenes, cryptoxanthin, lycopene and alpha- and gamma-tocopherols and baseline information on dietary and other demographic and life-style factors among 1,364 subjects 35-69 years of age, who are participants in a chemoprevention trial on pre-cancerous lesions of the stomach in Venezuela. Males had lower levels of ascorbic acid, alpha- and beta-carotene and cryptoxanthin and higher levels of alpha-tocopherol than females. This finding was confirmed in non-smokers and non-drinkers. In females, but not in males, age was positively associated with levels of ascorbic acid, cryptoxanthin, alpha- and beta-carotene and gamma-tocopherol. Male tobacco users had lower plasma levels of ascorbic acid, alpha- and beta-carotene and cryptoxanthin than nonusers, and regular alcohol drinkers had a decreased plasma levels of beta-carotene compared with non-drinkers. Female tobacco users had lower levels of ascorbic acid and cryptoxanthin than non-users, and regular alcohol drinkers had lower levels of ascorbic acid and lycopene than non-drinkers. Frequencies of consumption of fresh fruits, fruit juice, raw vegetables and plantains showed weak positive associations with plasma levels of several vitamins studied in both sexes. Sex, age in females, tobacco and alcohol use and dietary consumption affected plasma anti-oxidant vitamin levels in this population significantly. These factors may influence the effect of anti-oxidant treatment in intervention trials.

Adult↗
PubMed1996

Antioxidants, Helicobacter pylori and stomach cancer in Venezuela.

A randomized chemoprevention trial on precancerous lesions of the stomach is being conducted in Tachira State, Venezuela. The aims of the study are to evaluate the efficacy of vitamin supplementation in preventing the progression rate of precancerous lesions. Here we report on the pilot phase of the study in which two antioxidant preparations were evaluated on their ability to raise antioxidant levels in plasma and in gastric juice. The study aimed also to determine the antibiotic sensitivity profiles of Helicobacter pylori isolates prevalent in the area. Forty-three subjects with precancerous lesions (chronic gastritis, chronic atrophic gastritis, intestinal metaplasia and dysplasia) of the stomach were randomized to one of two antioxidant treatments. Treatment 1 (250 mg of standard vitamin C, 200 mg of vitamin E and 6 mg of beta-carotene three times a day) or treatment 2 (150 mg of standard vitamin C, 500 mg of slow release vitamin C, 75 mg of vitamin E and 15 mg of beta-carotene once a day) for 7 days. Blood levels of total vitamin C, beta-carotene and alpha-tocopherol and gastric juice levels of ascorbic acid and total vitamin C were measured before and after treatment on day 8. Both treatments increased the plasma levels of total vitamin C, beta-carotene and alpha-tocopherol/cholesterol but not those of ascorbic acid or total vitamin C in gastric juice. Treatment 1 was the best choice and resulted in a greater increase in the plasma levels of beta-carotene and alpha-tocopherol. H. pylori was cultured from 90% of the gastric biopsies; 35 isolates were identified which were highly resistant to metronidazole, a front-line antibiotic recommended against H. pylori in other settings.

Adult↗
PubMed1996

Prevalence of precancerous lesions of the stomach in Venezuela.

Gastric biopsies from 1477 participants in a chemoprevention trial for precancerous lesions of the stomach in Venezuela were evaluated for the prevalence of precancerous lesions and Helicobacter pylori infection. These study subjects were selected from participants in an early detection program for gastric cancer using double-contrast X-ray. Overall, 94% had some type of chronic gastritis (CG) and were positive for H. pylori using Giemsa stain, 49% had atrophic gastritis, 34% had intestinal metaplasia (IM), and 6.5% had dysplasia. There were only three subjects (0.2%) with normal gastric mucosa, and 4% had only superficial gastritis. The prevalence of all of these precancerous lesions increased with age, but there was no clear difference by gender. The prevalence of the various lesions was higher in the antral mucosa than in the fundic mucosa. H. pylori infection was strikingly frequent in our study population, with prevalence rates ranging from 73% in subjects with superficial gastritis to 95% in those with atrophic gastritis and IM and 98% in those with CG. The prevalence of H. pylori was equally high in males and females, and it was significantly positively associated with the degree of infiltration of poly- and mononuclear cells and with that of active regeneration; it was inversely correlated with the degree of atrophy, IM, and dysplasia. Our findings support the precancerous nature of the various gastric lesions and the etiological role of H. pylori infection in CG.

Adult↗
PubMed1996

Chemoprevention trial on precancerous lesions of the stomach in Venezuela: summary of study design and baseline data.

A double-blind, placebo-controlled trial is being conducted in a population at high risk for gastric cancer in Venezuela. The main aim of the trial is to assess the effect of antioxidant vitamins (beta-carotene, vitamin C and vitamin E) in blocking the progression of precancerous lesions of the stomach. Within the framework of a screening programme for stomach cancer, 2200 subjects of 35-69 years of age have been recruited. At study entry, a dietary questionnaire was completed, and gastroscopy with the collection of seven gastric biopsies was performed. After baseline examinations, the study participants were randomized to receive antioxidant treatment or placebo for three years. The treatment phase will be completed in mid-1998. At the end of the treatment phase, the investigations performed at study entry will be repeated. Before the initiation of the trial, various pilot studies were carried out that showed an extremely high prevalence of Helicobacter pylori infection (over 90%). Two eradication trials using anti-H. pylori treatments that give good results in Europe and North America gave very poor results in our study population. The low eradication rates achieved (5-20%) suggest a high prevalence of antibiotic-resistant H. pylori strains or high reinfection rates. These disappointing results led to deletion of an anti-H. pylori treatment phase of the main trial.

Adult↗
PubMed1992

Amiodarone pulmonary toxicity--three unusual manifestations.

Amiodarone is very useful treatment for refractory arrhythmias. However, it has a wide profile of adverse effects involving a number of organ systems. Pulmonary toxicity is the most serious of these side effects and often limits its clinical use. Three patients with unusual forms of amiodarone pulmonary toxicity are described. One had extensive unilateral alveolar disease, another pleural effusion, and in a third the pulmonary infiltrate improved with oral corticosteroids despite continuation of amiodarone therapy. Extensive unilateral alveolar disease and resolution of the pulmonary toxicity with corticosteroids despite continuing with amiodarone have not been previously reported. Pleural effusion has been noted only rarely. With the increasing use of amiodarone, pulmonary toxicity is likely to occur more frequently and it is important to be aware of its less common manifestations.

Adrenal Cortex Hormones↗
PubMed1989

Sexual conquest and patterns of black-on-black violence: a structural-cultural perspective.

In this article the structural-cultural perspective is offered as an alternative theoretical model to explain the etiology of specific patterns of black-on-black violence that occur as a result of lower-class black male adherence to norms that emphasize sexual conquest. The theory is a multifactor argument that assumes that there are specific types of black-on-black violence occur because of black exposure to racially induced structural pressures and dysfunctional cultural adaptations to those pressures. Because few studies examine the intrapersonal and interpersonal dynamics of black-on-black violence, this discussion of the structural-cultural perspective is grounded on findings and inferences from product (Wolfgang-type) studies of criminal violence and ethnographic accounts of lower-class black communities throughout the United States.

Black or African American↗
PubMed1985

The relative bioavailability of paracetamol and codeine after oral administration of a combination of buclizine, paracetamol and codeine, with or without docusate, and of paracetamol alone in healthy volunteers.

A randomized, double-blind, crossover study was carried out in 10 healthy volunteers to investigate whether the inclusion of the wetting agent docusate sodium (10 mg) in a combined oral formulation ('Migraleve') with buclizine hydrochloride (6.25 mg), codeine phosphate (8 mg) and paracetamol (500 mg) had any effect on the bioavailability of the analgesics. On 3 occasions at weekly intervals, the subjects were given 2 tablets of the standard formulation, the combination without docusate or 500 mg paracetamol alone. Blood samples were taken before and at fixed times during the 4 hours after administration of each preparation for estimation of plasma concentrations of paracetamol, by gas-liquid chromatography, and of codeine, by radioimmunoassay. The results showed that there were no significant differences between the mean paracetamol concentrations achieved after administration of each of the 3 preparations at any of the time points. Peak paracetamol plasma concentrations were 11.25 +/- 1.74 micrograms/ml at 0.5 hours, 9.6 +/- 1.04 micrograms/ml at 0.75 hours, and 9.53 +/- 1.66 micrograms/ml at 0.5 hours, respectively, after the standard formulation, the combination without docusate, and paracetamol alone. Mean elimination half-lives for paracetamol were 2.83 +/- 0.51, 1.92 +/- 0.20 and 2.49 +/- 0.46 hours, respectively, and the differences were not significant. The difference between mean plasma concentrations of codeine after the two preparations including this analgesic bordered on significance at 3 hours and was significant at 4 hours, but the areas under the curve were not significantly different. Peak codeine plasma concentrations after the standard formulation were 42.1 +/- 9.4 ng/ml at 0.75 hours compared with 36.9 +/- 3.4 ng/ml at 1.5 hours after the combination without docusate.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed1984

Changes in airway permeability and responsiveness after exposure to ozone.

The purpose of this investigation was to examine the relationship between airway responsiveness and the permeability of histamine through the airways in conscious sheep after exposure to ozone (O3). Airway responsiveness was assessed by measuring the change from baseline in mean pulmonary flow resistance following a controlled 2-min inhalation challenge with 1% histamine, containing 200 microCi/ml of [3H]histamine. The rate of appearance of the [3H]histamine in the plasma during inhalation challenge was used to estimate airway permeability. To perturb the airways, conscious sheep were exposed to either 0.5 or 1.0 ppm O3 for 2 hr via an endotracheal tube. Airway responsiveness and airway permeability were measured prior to and 1 day after exposure. In six sheep exposed to 0.5 ppm O3, increased airway responsiveness and airway permeability were observed 1 day after exposure. Four of seven sheep exposed to 1.0 ppm O3 had enhanced airway responsiveness and airway permeability, while the remaining three sheep showed corresponding decreases in airway responsiveness and airway permeability. Since the O3-induced directional changes in airway responsiveness paralleled the directional changes in airway permeability in both the positive and negative directions, it was concluded that changes in airway responsiveness to inhaled histamine following exposure to O3 may be related to concomitant changes in airway permeability to this agent.

Airway Resistance↗