Effect of vitamin C upon gastric mucosal O6-alkyltransferase activity and on gastric vitamin C levels.

The repair enzyme O6-alkyltransferase will repair O6-methylguanine adducts in human DNA. In gastric mucosal DNA these adducts may be formed as a result of exposure to nitrosamines within the gastric lumen. The formation of these nitrosamines may be inhibited by vitamin C. We have examined the effect of oral vitamin C supplementation upon intragastric vitamin C levels and gastric mucosal O6-alkyltransferase levels in 48 patients. Intragastric vitamin C levels were significantly elevated in those patients with normal gastric mucosal histology after treatment, although a variable response in intragastric vitamin C to supplementation was seen in the presence of chronic atrophic gastritis. Gastric mucosal O6-alkyltransferase activities ranged from 100 to 950 fmol/mg protein before vitamin C administration. The range of enzyme activity was similar after the course of vitamin C (62-1137 fmol/mg) but O6-alkyltransferase activities were found to be higher in 33 of the 48 patients following treatment (P < 0.01). Once again this effect was more pronounced in patients with normal gastric mucosa than those displaying evidence of chronic atrophic gastritis. We speculate that inhibition of intragastric nitrosation by vitamin C results in decreased formation of O6-methylguanine-DNA. In consequence, less O6-alkyltransferase is consumed in repairing these adducts resulting in higher tissue levels of this enzyme.

DNA damage as measured by 32P-postlabelling in normal and pre-malignant gastric mucosa.

DNA was extracted from the gastric mucosa of 69 patients and analysed for the presence of DNA adducts by 32P-postlabelling. Adduct levels found in patients with histologically normal gastric mucosa were compared with levels found in patients displaying evidence of chronic atrophic gastritis or intestinal metaplasia, both of which may be considered pre-malignant conditions. Adduct patterns were the same for all patients, but the highest adduct levels were found in the latter two groups. Mean adduct levels were also higher in patients with abnormal gastric mucosa, but there was no statistically significant difference in adduct levels between the normal and pre-malignant groups (P > 0.05, Mann-Whitney U test). Thus DNA adduct levels do not correlate with the presence of histological abnormalities in the stomach and are not useful as a marker of malignant potential.

Effect of vitamin C supplementation on gastric mucosal DNA damage.

The effect of oral vitamin C supplementation on intragastric ascorbate levels and gastric mucosal DNA damage as measured by the 32P-postlabelling assay was assessed in 43 patients. In patients with normal gastric mucosa, treatment with vitamin C resulted in elevation of intragastric ascorbate levels in all cases. In the presence of chronic atrophic gastritis, however, the effect was variable. Gastric mucosal DNA damage was decreased in 28 of the 43 patients after vitamin C supplementation (P = 0.01; Wilcoxon sign rank test). This supports epidemiological evidence that suggests vitamin C may exert a protective effect against the development of gastric cancer.

DNA damage in the stomach after vagotomy measured by 32P-postlabelling.

This study analysed gastric mucosal DNA by 32P-postlabelling in a series of patients who have had previous vagotomy for benign peptic ulcer disease. DNA adduct levels were found to be significantly higher in patients who had had previous truncal vagotomy than in those who had had previous highly selective vagotomy (p < 0.001). Intragastric bile concentrations were also considerably higher in patients after truncal vagotomy but there was no correlation between intragastric bile concentrations and DNA adduct levels. These results suggest that, although duodenogastric reflux may be a cause of gastric mucosal DNA damage in the stomach after vagotomy, measurement of total intragastric bile does not accurately reflect genotoxic insult.

O6-alkyltransferase activity in normal and abnormal gastric mucosa.

The activity of the DNA repair enzyme O6-alkyltransferase has been studied in a series of stomachs with abnormal gastric mucosa and the activities found compared with those in normal stomachs. Enzyme activities found in stomachs with the macroscopic abnormalities of gastric ulcer, duodenal ulcer or gastric cancer were not significantly different from normal. In those stomachs where there was histological evidence of chronic atrophic gastritis or intestinal metaplasia however enzyme activities (mean 398 fmole/mg) were significantly higher than normal (mean activity 228 fmole/mg activity P < 0.001). We speculate that the conditions which stimulate these histological changes also give rise to induction of O6-alkyltransferase.

Smoking-related DNA adducts in human gastric cancers.

DNA was extracted from the tumour tissue of 26 patients (18 smokers, 8 non-smokers) undergoing surgery for gastric cancer, and analyzed for the presence of DNA adducts by the 32P-post-labelling method. Adducts were detected in all samples tested, and adduct levels ranged from 2 adducts/10(8) nucleotides to 60 adducts/10(8) nucleotides. In male subjects, adduct levels were significantly greater in the DNA of smokers than in that of non-smokers. These results support epidemiological data suggesting that smoking is a risk factor for gastric cancer.

Relationship of self-efficacy and binging to adherence to diabetes regimen among adolescents.

OBJECTIVE: To test the hypothesis that poorer adherence to diabetes care is related to four variables associated with self-concept in adolescents with diabetes: self-esteem, self-efficacy, depression, and binging behavior. In addition, we expected adolescent females to be less adherent to diabetes care. RESEARCH DESIGN AND METHODS: We recruited 193 consecutive patients (aged 13-18 yr) with insulin-dependent diabetes mellitus during their regular quarterly visit to a diabetes clinic in a large urban hospital. Participants completed the Rosenberg Self-Esteem Scale, the Children's Depression Inventory, an assessment of the frequency of binging in the past 3 mo, and parallel forms of an adherence scale and a self-efficacy scale that were developed for use in this study. RESULTS: Adolescents who reported lower adherence tended to report lower self-esteem (r = 0.45, P less than 0.001) and self-efficacy (r = 0.57, P less than 0.001), more depressive symptoms (r = -0.50, P less than 0.001), more binging (r = -0.36, P less than 0.001), and had higher HbA1c (r = -0.24, P less than 0.001) than those with higher adherence scores. Together, the psychological variables accounted for 50% of the variance in adherence. There was no sex difference in reported binging, but, as expected, adolescent females reported less adherence overall (F[7,184] = 2.5, P = 0.018). CONCLUSIONS: Treatment adherence in adolescents with insulin-dependent diabetes mellitus is associated with behavioral and psychological variables. These findings suggest that specific behavioral and cognitive interventions could be used to improve adherence in those individuals who lack confidence in their ability to perform diabetes-related tasks.

Cyclosporine-associated organic mental disorders in liver transplant recipients.

The cases presented here, along with a preliminary body of clinical literature, suggest that, in conjunction with other factors, cyclosporine has an etiologic role in the production of a variety of organic mental disorders, including delirium, generalized anxiety disorder, hallucinosis, and organic mood disorder-depressed. The cases in this report were chosen in part because they illustrate definable organic syndromes. Other transplant recipients may experience less severe or isolated symptoms, such as sleep-wake reversal, insomnia, anxiety, lethargy, or mild confusional states that do meet full criteria for organic mental syndrome but that appear to be related to cyclosporine. Persecutory delusions may also occur in both floridly delirious patients and in patients with only minimal disorientation. Mental state aberrations most commonly begin within 2 weeks of treatment with cyclosporine, and, frequently, most acute symptoms resolve within a few weeks of onset. However, in more severely delirious patients or in patients with medical courses complicated by other problems, symptoms may continue longer. In particular, difficulties with memory and with the acquisition of new information may persist for several weeks. Less commonly, mental syndromes may also occur following longer periods of treatment with cyclosporine. Individual vulnerability appears to vary widely, and many patients demonstrate mental complications at cyclosporine levels that are in the moderate therapeutic range for immunosuppression. In addition, patients who have recently been started on cyclosporine and who demonstrate high therapeutic, rapidly rising, or toxic serum levels may be at greatest risk. Other risk factors may include intravenous administration, hypomagnesemia, hypocholesterolemia, and concurrent methylprednisolone bolus.(ABSTRACT TRUNCATED AT 250 WORDS)

O6-alkyltransferase activity in normal human gastric mucosa.

The spectrum of activity of the DNA repair enzyme O6-alkyltransferase has been studied in a large series of normal stomachs in order to establish the baseline range of values for this enzyme. Sixty-eight patients with histologically normal stomachs were biopsied during the course of upper gastrointestinal endoscopy and the biopsies assayed for O6-alkyl-transferase activity. A wide spectrum of activity was found with values ranging from 38 fmol O6-guanine extracted/mg protein to over 400 fmol/mg. This suggests that there may be wide inter-individual differences in susceptibility to alkylating actions in the human gastric mucosa.

Psychiatric, psychosocial, and rehabilitative aspects of lung transplantation.

The psychosocial assessment of applicants to the Toronto Lung Transplant Program provides the team with a variety of information including coping style; adjustment to illness; presence and management of psychiatric disorders; ability to adhere to medical recommendations; and available social support. This information facilitates the organization of resources to match each patient's strengths and vulnerabilities. The period of awaiting transplantation may be prolonged, and is often associated with high levels of anxiety. A support group, brief individual and family psychotherapies, and pharmacologic interventions have each been useful in ameliorating symptoms of stress during this time. A physical rehabilitation program is prescribed to most candidates and contributes to improved physical endurance as well as emotional well-being. Postoperative delirium has commonly occurred in lung transplant recipients, and appears to be associated with prolonged cardiopulmonary bypass when used, the administration of cyclosporine, and other nonspecific factors. Delirium has been managed with preoperative psychologic preparation and a routine postoperative protocol using intravenously administered haloperidol. Other immunosuppressant-associated organic mental disorders have also occurred in recipients. Postoperative recovery and rehabilitation are facilitated by both the preoperative exercise program and a postoperative exercise regimen. Recovery following transplant may require abrupt adjustment to new activity levels and reintegration into social and vocational roles. After 7 months, over 50% of surviving recipients have returned to employment and most report high satisfaction with physical and emotional well-being.

Assessment and management of psychosocial stress in lung transplant candidates. Toronto Lung Transplant Group.

Candidates for lung transplants have had their lives significantly disrupted, both by life-threatening lung disease and by involvement with a transplant program. The assessment and management of psychosocial distress as it has occurred in lung transplant candidates is described. Experience suggests that an informal social support network has been invaluable but is best complemented by formal interventions. Involvement with these candidates requires that the social worker be attuned to the unique circumstances and experiences of lung transplantation.

Postoperative organic mental syndromes in lung transplant recipients. Toronto Lung Transplant Group.

Delirium and other organic mental syndromes have frequently complicated the postoperative course of lung transplant recipients. A retrospective survey of 30 single-lung, double-lung, and heart-lung transplantations was undertaken to investigate the frequency of postoperative delirium, the responsible causative factors, and the efficacy of management strategies. Seventy-three percent of all recipients demonstrated an episode of delirium during their first 2 postoperative weeks. Undergoing cardiopulmonary bypass, having higher cyclosporine levels, and moving one's home from a distant location to await surgery were associated with an increased risk of postoperative delirium. A protocol that uses the intravenous administration of haloperidol has proved both effective and safe in the management of this frequently problematic complication.

Influence of functional impairment and social support on depressive symptoms in persons with diabetes.

Tested the buffering model of social support among 158 adults with diabetes. We predicted that, among patients with higher levels of illness-related impairment, adequate social support would act as a buffer against depression. Measures included the Beck Depression Inventory; the Sickness Impact Profile; and an assessment of the adequacy of social support to enable the patient to deal with illness-related tasks, domestic chores, financial responsibilities, and emotional needs. Depressive symptoms correlated positively with functional impairment (r = .58, p less than .001) and negatively with the adequacy of social support (r = -.31, p less than .001). In addition, social support moderated depression in the face of greater impairment such that, among patients who reported the most illness-related functional disabilities, adequate support provided a relative protection from depression. The findings suggest that individuals with inadequate support are most at risk to become depressed when disability related to illness increases.

Meditation and psychotherapy.

Meditation has been increasingly recommended as a practice with potential psychotherapeutic benefit. This paper provides a description of meditative practice and discusses selected issues related to the conceptual and technical integration of meditation with modern psychotherapeutic interventions. Evidence suggests that meditation may contribute to psychotherapeutic change and that the disciplines from which meditation arises are in some respects similar to modern psychological formulations, and in other respects are complimentary. It is hoped that improved understanding of meditation will contribute to an increased acceptance and use of these practices as aids to psychotherapeutic change and will facilitate meaningful research regarding meditation.