PubMed Health⌕ Search

Biomedical subjects

T Hofer

Publications and source records attributed to T Hofer.

34 records · Page 2Linked to original sources
PubMed1998

Reduction of oxidation during the preparation of DNA and analysis of 8-hydroxy-2'-deoxyguanosine.

The promutagenic base 8-hydroxy-2'-deoxyguanosine (8-OH-dG) in DNA is known to be formed from oxygen radical attack on 2'-deoxyguanosine (dG) as a result of oxidative stress. Formation of 8-OH-dG from dG during workup is strongly dependent on temperature and transition metals and is mediated by oxygen radicals. The 8-OH-dG formation at temperatures between 0 and 140 degrees C for 1.5 h in an "ultrapure" solution followed a third-order equation. Fe2+ in the nM range mediated the formation of 8-OH-dG from dG without addition of H2O2. Fe3+, Cu+, and Cu2+ were shown to have weaker oxidative effects in comparison to Fe2+. The pH (5.0-9.0) had a very limited effect on 8-OH-dG formation. Acid phosphatase, which contains iron at its active site, caused the formation of 8-OH-dG, whereas alkaline phosphatase did not. Phenol was not found to be oxidative. Fe2+-catalyzed formation of 8-OH-dG was completely blocked by the nitroxide 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO), whereas DMSO, mannitol, and DMPO had a significantly weaker protecting effect. Catalase cleaved the dG molecule and was not suitable for use. A simple, fast, and inexpensive method for 8-OH-dG workup and analysis was developed, and the background level seen in liver from 13-week-old male Sprague-Dawley rat was 0.23 +/- 0.020 8-OH-dG/10(5) dG, which is up to 200 times lower than reported values from some other methods and up to 26 times lower when compared to other reports using HPLC-EC methods. In summary, the TEMPO method reduces oxidation of dG to 8-OH-dG during workup by (1) using chemicals low in transition metals, (2) using a cold workup procedure, (3) limiting the incubation time, and (4) using the nitroxide TEMPO in all steps.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1998

Methodological considerations and factors affecting 8-hydroxy-2-deoxyguanosine analysis.

Oxidative stress is related to a number of diseases due to the formation of reactive oxygen species (ROS). There are also several substances found in the occupational environment or as life style related situations that generates ROS. A stable biomarker for oxidative stress on DNA is 8-hydroxy-2'-deoxyguanosine (8-OH-dG). A potential problem in the work-up and analysis of 8-OH-dG is oxidation of dG with false high levels as a result of analysis. This paper summarizes and discusses some of the critical moments in terms of auto-oxidation. The removal of transition metals, low temperatures, absence of isotopes (or 2'-deoxyguanosine) and incubation times are all important factors. Removal of oxygen is complicated while the problem is reduced if a nitroxide (TEMPO) is added during work-up. Certain reducing agents and enzymes could be critical if added during work-up. The application of the 32p-HPLC method to analyze 8-OH-dG is discussed. The 32P-HPLC method is suitable for 8-OH-dG analysis and avoids several factors that oxidizes dG by removal of dG before addition of isotopes. Factors of crucial importance (columns, eluents, gradients and detection of 32p) for the analysis of 8-OH-dG are commented upon and certain recommendations are made to make it possible to apply the 32P-HPLC methodology for this type of analysis.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1998

Interpreting risk-adjusted length of stay patterns for VA hospitals.

OBJECTIVES: The Veterans Health System must become more competitive with the private sector in terms of efficiency of care. Studies have shown significantly longer lengths-of-stay (LOS) in facilities operated by the Department of Veterans Affairs (VA) compared with private sector facilities. Most comparisons, however, have not controlled well for casemix differences or have involved small numbers of patients. The aims of this study were: (1) controlling for casemix, to accurately measure the degree by which average length of stay in Veterans Affairs facilities exceeds that of private sector hospitals and (2) to demonstrate a methodology with which individual VA facilities can identify clinical and demographic subgroups of patients associated with the higher length-of-stay averages. METHODS: Subjects of the study were Veterans Health System patients hospitalized during 1991-1993 and veteran respondents to the 1991 National Hospital Discharge Survey. Hospitals' mean length of stay adjusted for patients' diagnosis related groups, severity, demographics, and travel distances were measured. RESULTS: Veterans Affairs medical centers' average risk-adjusted length of stay was 36% higher (8.9 days compared with 6.5 days) than that of the private sector. For individual hospitals, relative length-of-stay efficiency typically varied by condition. Among 14 hospitals in the VA's midwest region, none were high risk-adjusted length-of-stay outliers in all conditions studied, and four were high outliers for some conditions and low outliers for others. CONCLUSIONS: Controlling for differences in patient demographic and clinical factors, Veterans Affairs medical centers consumed significantly more days of care than private sector hospitals. Veterans Affairs medical centers will be able to improve efficiency by identifying specific subgroups of patients whose clinical treatment should be examined.

Comorbidity↗
PubMed1998

[Responsibilities of psycho-oncology].

Psychooncology is the application of the biopsychosocial concept with cancer patients. Advising the patient and his circle of relatives and friends in crises, discussing topics important to the patient and negotiating in difficult situations makes it possible for the patient and his relatives and friends to take active part in coping with the illness. This also serves to relieve nurses and physicians in their care of the patient.

Adaptation, Psychological↗
PubMed1997

How not to miss a somatic needle in the haystack of chronic pain.

Interviews with 18 male patients with predominantly psychogenic pain (DSM-III and DSM-III-R) and with 18 male patients with pain of mainly physical origin, consecutively admitted to a medical department, were rated by blinded and independent raters with respect to "symptom description," "manner of speech," "personality characteristics," "interviewer reactions," "interpersonal relationships," and "relationships at work." Patients with predominantly organic pain significantly more often described a clear localization of the pain symptom, used more sensory words for the description of pain quality; more often described discrete changes of pain intensity and periodicity; more often showed pain-intensifying factors dependent on movement and pain-decreasing factors; more often believed pain to be a symptom versus as a disease itself, and tended to have fewer difficulties in their interpersonal relationships than those with predominantly psychogenic pain (p < 0.05 for all factors, two-tailed Fisher's Exact test).

Adult↗
PubMed1997

[32P]ATP mediates formation of 8-hydroxy-2'-deoxyguanosine from 2'-deoxyguanosine, a possible problem in the 32P-postlabeling assay.

8-Hydroxy-2'-deoxyguanosine (8-OH-dG) is a biomarker for oxidative stress on DNA, a common lesion in mammalian cells. A correlation between increased levels of 8-OH-dG and diseases like diabetes, infections and cystic fibrosis has been found in humans. 8-OH-dG levels have been shown to be decreased by antioxidants, an indication of the importance of dietary habits. 8-OH-dG is used as a biomarker for oxidative stress in vivo as well as in vitro and is suggested to be a mutagenic DNA lesion. Different methods are used for the analyses of 8-OH-dG, i.e. GC-MS, HPLC-EC and 32P-postlabeling. The most commonly used method is HPLC-EC. In the analysis of 8-OH-dG, the work-up procedure for DNA, as well as the preparation for analysis, are of critical importance as there is a risk for auto-oxidation of deoxyguanosine (dG), which would result in false high background levels and low sensitivity in analysis. 32P-Postlabeling has recently been applied to the analysis of 8-OH-dG and has shown to be a very sensitive method for the detection of DNA adducts. It is shown here that after extrapolation to normal 32P-postlabeling conditions, [32P]ATP generated 8-OH-dG to levels of 25 8-OH-dG/10(5) dG. [32P]ATP mediated the formation of 8-OH-dG from dG in a dose-dependent manner at all dose levels (0.13-12 microCi). The reaction occurred immediately and increased with time in a linear dose-response fashion. At high doses (6.0 and 12 microCi) the dose-response declined after 24 h, which indicates a possible decomposition or rearrangement of 8-OH-dG. A repeated experiment with 5 microCi [32P]ATP during 2 h resulted in a linear formation of 8-OH-dG and a level of 19 8-OH-dG/10(5) dG. The results indicated that awareness of the auto-oxidation generated by 32P[ATP] in the postlabeling assay is of utmost importance and that dG must be separated before 32P-postlabeling of 8-OH-dG.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1995

Enteral feeding tube placement success with intravenous metoclopramide administration in ICU patients.

OBJECTIVE: The purpose of this study was to determine if intravenous push metoclopramide would facilitate immediate transpyloric passage of a small-bore feeding tube without fluoroscopy or endoscopy. DESIGN: Prospective, randomized trial. PATIENTS: One hundred five medical and surgical ICU patients at a community teaching hospital. INTERVENTIONS: Patients were randomized to receive 10 mg of metoclopramide 10 min before tube insertion or no medication. MEASUREMENT: Successful placement was stated as radiologically verified transduodenal tube location. RESULTS: A 54% success rate was shown with administration of the drug with 46% success for the control. Chi square analysis of the success rate showed no significant relationship between administration of metoclopramide and successful tube placement (p = 0.38). Increasing years of physician training was the only variable associated with successful placement (p = 0.003). No association was found between successful tube placement and presence of endotracheal tube, tracheostomy, or cervical immobility, nor any interaction of metoclopramide with these variables. CONCLUSION: Intravenous metoclopramide, 10 mg, administered 10 min prior to intubation with a small-bore feeding tube (10F), was ineffective in facilitating transpyloric intubation.

Critical Illness↗
PubMed1994

Measuring physician attitudes toward cost, uncertainty, malpractice, and utilization review.

OBJECTIVE: To develop a reliable measure of physician attitudes postulated to influence resource utilization. DESIGN: Statements related to attitudes that may influence resource use were culled from the literature and informal discussions with physicians. SETTING: Academic medical center. PARTICIPANTS: All faculty and housestaff in internal medicine, pediatrics, family medicine, and surgery at an academic medical center were surveyed. The response rate was 59% (n = 428). RESULTS: Exploratory factor analysis of all internal medicine surveys revealed four prominent domains. These closely corresponded with our a-priori hypothesized domains and were interpreted as cost-consciousness, discomfort with uncertainty, fear of malpractice, and annoyance with utilization review. A replication of the analysis using 25 survey items and conducted on the remainder of the data (surgeons, pediatricians, and family practitioners) revealed a similar four-factor solution. Scales were constructed for each of the four domains. Cronbach's alpha ranged from 0.66 to 0.88. Discomfort from uncertainty and fear of malpractice were moderately correlated (r = 0.42); other scale-scale correlations were modest. Of the four attitude measures, only cost-consciousness was associated with lower self-estimates of resource use. Both annoyance with utilization review and fear of malpractice increased as the proportion of time spent in patient care increased. CONCLUSIONS: Although various physician attitudes and beliefs have been hypothesized to influence health services resource use, reliable and valid measures for most of these have not been developed. The authors developed a 19-item survey instrument designed to measure these attitudes reliably. The four scales developed in this study may help identify physician attitudes that are important determinants of physician decision making and help foster a better understanding of physicians' reactions and acculturation to different practice environments.

Academic Medical Centers↗
PubMed1993

Glasgow scale relationships in pediatric and adult patients.

The purpose of this study was to examine the relationship of the Glasgow Coma Scale (GCS) and Glasgow Outcome Scale (GOS) scores in pediatric and adult patients having surgical entry into the cranium for diagnostic or therapeutic purposes after brain insult. In this retrospective record review, the predictor variable was the coma-associated GCS score (GCS score 3-8) obtained 24 hours after surgery. The outcome variable was the combined Glasgow Outcome category: recovery/moderate disability; severe disability/vegetative state; and death; ascertained 14 days postoperatively. Using discriminant analysis, the unweighted GCS scores for the total sample significantly discriminated two of the three GOS outcomes (p < .001); the weighted scores discriminated all three outcomes (p < .001). Considering the GCS components, the eye scores significantly discriminated one outcome, the motor scores two outcomes, and the verbal scores two outcomes (p < .001 to .005). The unweighted GCS scores in adults significantly discriminated all three outcomes and in children two outcomes; the weighted GCS scores in both children and adults significantly discriminated all three outcomes. The approximately 25% misclassification rate for outcomes, however, would preclude using the scales in a predictive or prescriptive manner.

Adolescent↗
PubMed1986

[Food allergies. III. Therapy: elimination diet, symptomatic drug prophylaxis and specific hyposensitization].

The treatment of food allergies is logically based on strict elimination of causative allergens. While it is easy to eliminate food which is infrequently consumed, it is more difficult to manage an allergy involving regularly consumed foods, especially where patients have to eat away from home for professional reasons. The creation of elimination diets for milk, eggs, and mould and yeast allergies is discussed. In raw food and vegetable allergy the act of cooking is often sufficient to denature the allergen as it is unstable to heat. Follow-up investigations show that some 50% of children achieve cure spontaneously by strict elimination diet, especially in regard to milk allergy. In our own 173 (mainly adult) patients with food allergy, some 2/3 reported after 3-5 years that a strict elimination diet had to be followed, since otherwise prompt relapse of allergic symptoms was noted. About 1/3 of patients, mainly with milk, cheese or egg allergy, can hope for spontaneous desensitization by appropriate diet. This is demonstrated by a case history with disappearance of IgE antibodies. Should this fail to occur, oral desensitization with milk or egg-white extracts offers an effective therapy. The practice of hyposensitization with foodstuffs is illustrated by examples and tabulation of immunologic parameters. In raw food or vegetable allergy, which is often associated with birch or mugwort pollinosis, improvement or even complete cure can be expected in about 1/3 of cases by systematic desensitization of pollinosis. On the other hand, the therapy and prognosis of food allergy involving extreme and polyvalent sensitivities, especially to spices, or with multifactorially induced symptoms, is more problematic. In these cases a strict elimination diet should be followed by continuous prophylactic/symptomatic treatment with antianaphylactic substances such as cromoglicinic acid (Nalcrom) - especially in gastrointestinal food allergies - or with ketotifen (Zaditen) or oxatomide (Tinset) in hematogenically released shock fragments. Patients with severe anaphylactic reactions after meals should, by analogy with patients with hymenoptera allergy, carry an emergency kit containing an adrenaline spray (Medihaler-Epi), a soluble corticosteroid (e.g. Betnesol) and anthistaminic drugs (e.g. Tavegyl, Teldane).

Adult↗
PubMed1985

[Food allergy. II. Prevalence of organ manifestations of allergy-inducing food. A study on the basis of 173 cases, 1978-1982].

From 1978 to 1982 173 cases of food allergy were diagnosed at the Allergy Unit of the Dermatological Clinic, University of Zürich. Of these predominantly adult patients, 118 (68%) were female and 55 (32%) male. 65% of the food-allergic patients also showed one or more atopic manifestations, and 26% pollinosis. Localization of symptoms of food allergy was most often the skin (43%), followed by the respiratory tract (23%), the gastrointestinal tract (21%) and the cardiovascular system (12.5%). Only 11% had exclusively intestinal allergic reactions. The most frequent food allergens were found to be vegetables. Celery headed the list with 40.5%, followed by carrots (20%) and green beans (6%). Other commonly occurring food allergens were eggs (21%), milk and dairy products (20%) and fish (12%). Sensitivity was found to groups of raw vegetables, and also cross-reactivity to other nutritional and inhalative allergens. In view of this finding the term "celery-carrot-mugwort-spice-syndrome" was coined. Regarding diagnostic procedure, a precise history remains essential. Once again, scratch techniques performed with fresh raw food proved to be markedly more dependable than skin tests performed with commercial food extracts. The use of a RAST was especially helpful in diagnosing milk-cheese-casein allergies.

Adolescent↗
PubMed1984

[Food allergy: the celery-mugwort-spice syndrome. Association with mango allergy?].

Celery allergies are commonly observed in mugwort pollen-allergic patients. This situation is frequently associated with an allergy to spices of the umbelliferous family. Thus a "celery-mugwort-spice syndrome" has been established. In 31 patients (27 females, 4 males) allergy to celery was diagnosed between 1978 and 1982. They were followed up in 1983 and complementary tests (skin and RAST) with various raw vegetables, spices and mugwort pollen were done. For specific diagnosis of allergy to celery skin testing (scratch or prick) with fresh celery bulb was reliable. In contrast, RAST was not sufficiently sensitive, 87% of patients allergic to celery had pollinosis in the form of mugwort pollen sensitisation established by skin testing and RAST. Allergy to carrots was clinically and by testing currently associated in 52%. In contrast, a clinically relevant hypersensitivity to caraway (26%), parsley (16%), fennel (13%), green pepper (10%) and aniseed (3%) was found less frequently although these allergens showed a much larger positivity in skin testing. This signifies group sensitisation within the umbelliferous plants. The association of celery-mugwort allergy with allergy to mango fruit described here for the first time cannot be explained as group sensitisation within a botanic relation, as mango, and pistachio-nut, belong to the family of anacardiaceae.

Adolescent↗
PubMedDate not supplied

Designing a simpler high blood cholesterol case detection strategy: are the advantages of the NCEP protocol worth the complexity?

OBJECTIVE: To determine whether the complex strategy of lipid measurements for the detection of patients with high blood cholesterol levels proposed by the first Expert Panel of the National Cholesterol Education Panel (NCEP) could be simplified without significant loss of accuracy. DESIGN: Decision-analysis-based model of competing case detection strategies as compared with the NCEP strategy. A Markov model was used to estimate numbers of people treated over ten years as a result of the different classification strategies. DATA SOURCES: Conditional probabilities for the decision trees were derived from cholesterol distributions in national population-based surveys. Parameters for the Markov model were from published major epidemiologic studies and clinical trials. MAIN OUTCOME MEASURES: Misclassification to treatment vs non-treatment as a continuous function of the distribution of true low-density lipoprotein (LDL). RESULTS: A simplified strategy was designed that screens high-risk persons with two LDL measurements and low-risk people with one cholesterol measurement followed by two LDL measurements if the initial value is high. This algorithm requires 37% fewer measurements to classify a population. The overall accuracy of classification to treatment based on the NCEP I cutoff points is high, with a positive predictive value of 95% and a negative predictive value of 87% (relative to 97% and 80%, respectively, for the NCEP I protocol). This strategy is very similar to published NCEP II guidelines. A strategy that recommends an LDL determination for everyone, as a recent NIH consensus panel suggested, also significantly reduces the number of measurements required by 48%. The positive predictive value is 93%, vs 97% for the NCEP I protocol. The negative predictive value is 92%, vs 80% for the NCEP I. CONCLUSIONS: The complex measurement strategy initially proposed in the NCEP I guidelines did not improve accuracy of classification over the simpler and more convenient strategies that the authors evaluated and that have been substantially adopted in the NCEP II guidelines.

Adult↗