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Biomedical subjects

S Graham

Publications and source records attributed to S Graham.

At least 127 records · Page 7Linked to original sources
PubMed1993

A study of the dose dependency of a glycine receptor antagonist in focal ischemia.

N-methyl-D-aspartate receptor antagonists are potent neuroprotectants in experimental focal cerebral ischemia, but behavioral and neuropathologic changes seen with these drugs in rodent models may limit the clinical utility of these compounds. Glycine's modulation of N-methyl-D-aspartate channel function offers another pharmacologic approach to excitotoxicity in ischemia. The potent glycine antagonist 7 Chlorothiokynurenic acid (7-Cl-Thio-Kyna) was studied in a permanent middle cerebral artery occlusion stroke model in the rat. The compound was effective, in a dose-dependent manner, in attenuating infarct size when administered before or after permanent middle cerebral artery occlusion. Its activity was mainly due to glycine antagonism inasmuch as 5 Chlorothiokynurenic acid, a compound having other pharmacological activities in common with 7-CI-Thio-Kyna (for instance the radical scavenger action), was inactive in this model. 7-Cl-Thio-Kyna did not produce cytological changes similar to MK 801.

Animals↗
PubMed1993

Frequency of changing enteral alimentation bags and tubing, and adverse clinical outcomes in patients in a long term care facility.

Enteral alimentation, given via nasogastric or gastrostomy tubes, is a well established practice to provide nutrition for patients with significant neurological injury. The frequency with which enteral feeding bags and tubes require change and potential adverse effects associated with bacterial contamination of tube feeds remain controversial. The authors studied different times between enteral feeding bag and tube changes, and the effect on adverse clinical outcomes in residents of a long term care facility. In the first study, residents were randomized to 24 h (n = 2), 48 h (n = 3) or 72 h (n = 6) tube feeding and bag changes with clinical status monitored in a standardized fashion for six months. In the second study, patients were randomized to 24 h (n = 6) or 72 h (n = 6) changes. Patient-days of follow-up were 382, 574 and 1000 for the three arms of the first study period and 556 and 496 for the two arms of the second study. No differences in potential clinical adverse events--including fever, gastrointestinal symptoms or pneumonia--were observed with different durations of tubing change. This study suggests it is appropriate to change alimentation tube and feeding bags every 72 h (rather than every 24 h). The less frequent changes will decrease supply costs and free nursing time for other activities.

Aged↗
PubMed1993

An attributional intervention to reduce peer-directed aggression among African-American boys.

An attributional intervention was designed to reduce aggressive males' tendency to attribute hostile intentions to peers following ambiguously caused peer provocations. African-American elementary school boys (N = 101), aggressive and nonaggressive, were randomly assigned to the attributional intervention, an attention training program, or a no-treatment control group. Data were collected on subjects' attributions about hypothetical and laboratory simulations of peer provocation, disciplinary referrals to the school office, and teacher ratings of aggressive behavior. Aggressive subjects in the attributional intervention were less likely to presume hostile intent by peers in hypothetical and laboratory simulations of ambiguous provocation. They were also less likely to endorse hostile retaliation on judgment measures and to engage in verbally hostile behaviors in the laboratory task. Further, intervention subjects were rated as less aggressive by their teachers following the treatment. Both the benefits of attributional change and its limitations in the African-American population are discussed.

Achievement↗
PubMed1992

Diet in the epidemiology of postmenopausal breast cancer in the New York State Cohort.

A number of authors have presented evidence that high dietary fat increases the risk of breast cancer, and a number have presented evidence to the contrary. In this study, dietary histories were obtained in 1980 from 18,586 postmenopausal women in New York State. These women were followed through 1987 to ascertain their incidence of breast cancer and other cancers and deaths from all causes, as registered in the New York State Tumor Registry and Office of Vital Statistics. Survival analysis revealed that the incidence of breast cancer increased with age, was higher among the nulliparous, was higher for those with a late (> 26 years) age at first pregnancy, and increased with increasing socioeconomic status--all risk factors discovered before for breast cancer. No increase in risk was related to the ingested amount of calories, vitamins A, C, or E, dietary fiber, or fat. Although dietary fat has been found to be associated with higher risk of cancer at a number of other sites, e.g., the lung, colon, and rectum, and although some previous writers have suggested an association with risk of breast cancer, the findings in three cohort studies as well as in eight substantial case-control studies are negative and suggest that a relation is far from established.

Age Factors↗
PubMed1992

Phase II evaluation of fluorouracil and recombinant alpha-2a-interferon in previously untreated patients with pancreatic adenocarcinoma.

BACKGROUND: Based on initial encouraging results of the combination of 5-fluorouracil (5-FU) with recombinant alpha-2a-interferon (r alpha-2a-IFN) in the treatment of advanced colorectal carcinomas, a clinical trial was conducted using 5-FU with r alpha-2a-IFN in 49 patients with advanced pancreatic adenocarcinoma. METHODS: Forty-nine patients who had bidimensionally measurable disease and had not been treated previously with chemotherapy were entered in the trial. Starting on day 1, 5-FU was administered as a continuous infusion at a dose of 750 mg/m2/day for 5 consecutive days. Starting on day 12, it was administered as an intravenous bolus of 750 mg/m2 a week for 7 weeks. The r alpha-2a-IFN was administered subcutaneously at a dose of 9 x 10(6) units three times a week during weeks 1-8. RESULTS: Of the 46 patients evaluable for response, none had a complete response, and two had partial responses that lasted 14 and 28 weeks. The overall response rate was 4% (95% confidence interval, 1-15%). Fourteen patients had minor responses (median duration of response, 12 weeks). The median length of survival of all patients enrolled in this trial was 22 weeks. Grade 3-4 toxicities included oral mucositis in 19 patients, granulocytopenia in 16, fatigue in 8, and diarrhea in 3. One patient had severe ataxia and leg weakness. Another died of neutropenic sepsis. CONCLUSIONS: This regimen had significant toxicity and little evidence of therapeutic activity against advanced pancreatic carcinoma.

Adult↗
PubMed1992

Problem drug use in a central London general practice.

OBJECTIVE: To describe the profile of problem drug users presenting in general practice and to determine whether they can be cared for in general practice. DESIGN: Study of consultations by problem drug users. SETTING: Central London general practice. SUBJECTS: 150 problem drug users presenting over two years. MAIN OUTCOME MEASURES: Stopping drug use, alterations in lifestyle, obtaining paid work, and stopping drug related crime. RESULTS: Of the 150 patients, 111 were men and 39 women, and 106 were unemployed. 121 patients used heroin, 112 of whom injected. 145 patients accepted a methadone reduction programme and 81 completed it. A further 25 were stabilised on reducing doses of methadone, until places became available for them as inpatients at drug dependency units or rehabilitation projects. CONCLUSION: Withdrawal programmes for patients who misuse drugs can be successfully managed in general practice.

Family Practice↗
PubMed1992

Advantages of branched peptides in serodiagnosis. Detection of HIV-specific antibodies and the use of glycine spacers to increase sensitivity.

The reactivities of antibodies with branched and monomeric peptides were compared in ELISA assays. We found that lower amounts of antibodies could be detected with branched peptides than with monomeric peptides. This was observed with a monoclonal antibody and with antibodies in the sera of various HIV-positive individuals. To investigate the physical aspects of branched peptides important for the observed increase in sensitivity, glycine spacers of different lengths were introduced between the branched lysine core and the epitope reacting with the monoclonal antibody. The effect of the number of glycine residues, both on the sensitivity of antibody detection and on the amount of branched peptide needed to produce a given signal, was studied and the optimum was found at 4-5 residues. We discuss the basis for these findings and conclude that the routine use of branched peptides for serodiagnosis will give both greater sensitivity and appreciable cost savings.

AIDS Serodiagnosis↗
PubMed1992

Alcohol consumption and lung cancer in white males.

Experimental and epidemiologic investigations in alcoholic and nonalcoholic populations have suggested a role of alcohol in lung carcinogenesis. The association between alcohol consumption and lung cancer was investigated among 280 White males with histologically confirmed, primary lung cancer and 564 White male controls, participants in the Western New York Diet Study (United States). Among heavy smokers (over 40 pack-years), total alcohol consumption was associated with an increased risk of lung cancer with adjustment for age, years of education, pack-years of cigarette smoking, and intake of carotenoids and fat. In this group, the odds ratio for drinkers of more than 24 drinks per month was 1.6 compared with those who drank less. Drinkers of more than 12 beers per month were 1.6 times more likely to develop lung cancer than nondrinkers of beer after controlling for age, years of education, and cigarette smoking (95 percent confidence interval = 1.0-2.4, P for trend = 0.003). Occupational and dietary factors did not seem to explain these findings. Although cigarette smoking is the major cause of lung cancer, the role of alcohol, independent or in interaction with cigarette smoking, deserves further investigation.

Adult↗
PubMed1992

Comparative analysis of the immunostimulatory properties of different adjuvants on the immunogenicity of a prototype parainfluenza virus type 3 subunit vaccine.

The immunogenicity of a parainfluenza virus type 3 (PIV-3) subunit vaccine consisting of affinity-purified haemagglutinin-neuraminidase (HN) and fusion (F) surface glycoproteins was tested in guinea-pigs and hamsters. The ability of several different immunopotentiating agents to enhance the antibody response of animals to the PIV-3 surface glycoproteins was evaluated. The immunity induced by HN and F alone was compared with the response elicited by purified proteins combined with Freund's complete adjuvant, aluminium phosphate, Syntex's threonyl-muramyl dipeptide (MDP) SAF-MF formulation, or Ribi's adjuvant formulation containing BCG cell wall skeleton (CWS), trehalose dimycolate (TDM) and monophosphoryl lipid A (MPL) in a 2% squalene-in-water emulsion. Purified proteins were also incorporated into three different liposome formulations prepared by the detergent dialysis procedure. Immunization of guinea-pigs and hamsters with two 15 micrograms doses of the PIV-3 surface glycoproteins administered in the absence of adjuvant elicited high haemagglutination inhibition, neutralization and anti-fusion titres. The liposome preparations failed to enhance the antibody titres. Ribi's adjuvant formulation was effective at inducing a good secondary response to the purified proteins while the immunostimulatory effects of aluminium phosphate, Syntex and Freund's adjuvants were clearly demonstrated in both primary and secondary responses. When administered without adjuvant, a 15 microgram dose of the HN and F mixture was capable of protecting hamsters against live virus challenge. The immunoprotective dose of the purified proteins could be reduced to at least 0.1 microgram by the addition of aluminium phosphate, Syntex or Freund's adjuvants.

Adjuvants, Immunologic↗
PubMed1992

Smoking, alcohol, dentition and diet in the epidemiology of oral cancer.

This matched case-control study was conducted in Western New York. The smoking, alcohol consumption, dental hygiene and diet of 290 cases were compared with those of 290 sex-, age-, and neighbourhood-matched controls. The results confirm earlier findings that cigarette smoking and alcohol consumption impart substantial risk of oral cancer. The results also confirm that poor oral hygiene increases the risk of oral cancer, although this effect is much smaller than those of cigarette smoking and alcohol consumption. The results suggest that, of macronutrients, intake of fat is more likely than those of protein or carbohydrate to be related to risk. Of micronutrients, calcium, sodium, riboflavin and retinol are associated with risk, while thiamin, niacin, and dietary fibre are associated with decreased risk. Although patterns of dietary effects are discernable, these effects are in general much weaker than are those of smoking and alcohol consumption.

Aged↗
PubMed1992

Diet, smoking, and alcohol in cancer of the larynx: a case-control study.

A case-control study among white men in western New York was conducted from 1975 through 1985 to examine diet and other risk factors for laryngeal cancer. Incident pathologically confirmed cases (250) and age- and neighborhood-matched controls (250) were interviewed to determine usual diet and lifetime use of tobacco and alcohol. Cigarettes were strongly associated with risk; pipes and cigars were not. Beer and hard liquor but not wine were associated with increased risk. Dietary fat and carotenoids were related to risk in opposite ways. The upper quartile odds ratio for dietary fat was 2.40 [95% confidence interval 1.26, 4.55], and the upper quartile odds ratio for carotenoids was 0.51 (0.26, 1.01). There was effect modification by smoking. Carotenoids were most negatively associated with risk among the lightest smokers, whereas dietary fat was most positively associated with risk among the heaviest smokers. Total calories, protein, and retinol were associated with increased risk; there was no relationship between laryngeal cancer and vitamin C, vitamin E, carbohydrate, or dietary fiber. This study again demonstrates the strong association between tobacco and alcohol and laryngeal cancer and also suggests that diets low in carotenoids and high in fat may increase risk.

Aged↗
PubMed1992

Diet in the epidemiology of bladder cancer in western New York.

We present the dietary epidemiology of bladder cancer while controlling for a number of lifestyle and environmental risk factors in a study of 351 white male cases with histologically confirmed transitional cell carcinoma of the bladder and 855 white male controls selected from Erie, Niagara, and Monroe counties of western New York from 1979 to 1985. Usual diet was estimated by comprehensive interviews with use of a detailed food frequency questionnaire. An increased risk of bladder cancer was associated with higher kilocalorie intake, but only among those under 65 years of age, with the strongest pattern associated with fat intake. Further analyses of fat, carbohydrates, and protein, with adjustment for total kilocalories, resulted in a positive association of risk with fat intake and a decreasing risk with higher protein intake. Of the vitamins, carotenoid consumption appeared to decrease risk with increased consumption for those under 65 years of age. No significant differences between cases and controls were seen for intake of calcium, retinol, thiamin, riboflavin, niacin, vitamin C, vitamin D, and vitamin E. After adjustment for kilocalories and other confounders, higher intake of dietary sodium was associated with increased risk among both age groups, and the trends were statistically significant. The importance of diet in the etiology of bladder cancer is suggested by our findings.

Adult↗
PubMed1992

Dietary patterns and colon cancer in western New York.

Seven dietary patterns were identified among control subjects in the Western New York Diet Study (1975-1986) by application of principal components analysis to data from a 95-item food frequency interview. The results of case-control analyses of colon cancer risk for these patterns are presented. Cases were matched with neighborhood controls on the bases of age and sex; 205 colon case-control male and 223 female pairs were obtained. The dietary patterns and intakes of energy, total fat, and dietary fiber were examined with logistic regression for their individual contributions to risk. In males, three of these dietary patterns were associated positively with fat and energy consumption; they elevated risk for colon cancer and accounted for more risk than did the specific nutrients. Control for energy and fat intakes allowed the protective influences of additional dietary patterns to be expressed. No patterns elevated risk in women; two patterns were protective for colon cancer. Controlling for energy and fat intake enhanced the protection afforded by one of these patterns but had no influence on that of the other. Measures of foods rather than single nutrients may be more inclusive of dietary exposures to risk as well as being related more directly to underlying health behaviors. Therefore they may be better able to account for risk in diseases with multiple causation.

Case-Control Studies↗
PubMed1992

Immunodominant epitopes of HIV-1 p17 and p24.

Immunodominant antibody-binding sites were mapped using overlapping synthetic peptides of the structural proteins p17 and p24 of human immunodeficiency virus type 1 (HIV-1). Using sera from HIV-1-infected individuals at a variety of disease states, three major epitopes were identified within p17 and one within p24. Antibodies which recognized these epitopes were present in all risk groups throughout all stages of HIV infection, regardless of the presence of high levels of serum p24 antigen.

Amino Acid Sequence↗
PubMed1992

Monoclonal antibodies to the C4 region of human immunodeficiency virus type 1 gp120: use in topological analysis of a CD4 binding site.

We have raised antisera and monoclonal antibodies (MAbs) to the C4 region of HIV-1 gp120, using an antigen chimaera of poliovirus as immunogen. These MAbs and sera, together with MAbs to the same region raised by other methods, fall into three groups defined by their abilities to bind to recombinant gp120 and/or the immunogenic peptide. In some cases, the amino acids recognized by the MAbs have been identified by pep-scan and by solution phase peptide inhibition of binding to recombinant gp120. Our results indicate that the amino acids WQEVGKAMYA are exposed on the surface of recombinant gp120. Antibodies to these amino acids on recombinant gp120 compete for soluble CD4 binding in vitro, but only weakly neutralize HIV.

Amino Acid Sequence↗