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Biomedical subjects

M Gerber

Publications and source records attributed to M Gerber.

At least 37 records · Page 2Linked to original sources
PubMed2001

Diet profiles in a population sample from Mediterranean southern France.

OBJECTIVE: A Mediterranean diet quality index (MDQI) was devised to give an overall assessment of dietary habits and to identify groups at risk. DESIGN: The MDQI was based on scores given for selected levels of consumption of selected nutrients and foods. SETTING: Mediterranean southern France. SUBJECTS: The sample included 473 men and 491 women in three age classes recruited at random. RESULTS: Only 9.5% of men, 9.0% of women, 4.7% of 20-34 year old subjects, 6.6% of 35-54 year old subjects and 14.0% of 55-76 year old subjects were shown to have a healthy diet. However, 10.1% of men, 8.6% of women, 19.4% of 20-34 year old subjects, 10.2% of 35-54 year old subjects and 4.6% of 55-76 year old subjects were shown to have a poor diet. There were significantly fewer smokers among subjects with a good diet but the distribution of moderate wine drinkers was comparable between those with a good diet and those with a poor diet. Correspondence analysis associated a healthy diet with 55-76 year old men and women living in rural areas, who had received primary schooling only and who were manual workers. Both men and women with a poor MDQI score tended to be young and smokers. In addition, women with a poor MDQI tended to be heavy drinkers and obese. CONCLUSIONS: This study showed that the Mediterranean model, which is generally recognized as a healthy diet, appears restricted to older people and to rural areas, whereas urbanized young people depart from it. A nutritional prevention policy targeted at young adults is required to encourage them to adhere to the Mediterranean model. Smoking and drinking showed different distribution patterns in the sample under study.

Adult↗
PubMed2001

The comprehensive approach to diet: a critical review.

Recent disappointing results have challenged the earlier results of ecological studies that launched the hypothesis of a strong relationship between diet and cancer. The present state of knowledge regarding the relationship between cancer and diet is considered and discussed here. Steps for improving the understanding of the relationship and the content of recommendations for cancer prevention and survival are proposed, such as determining the possible food effect at each step of the carcinogenesis process, considering the dietary pattern instead of a single nutrient or food, introducing the diet quality index for evaluating cancer risk and developing more comprehensive statistical methods in nutritional epidemiology. In support of these propositions, previous, recent and on-going studies are reviewed and discussed. A holistic model of diet is described as a conclusion.

Diet↗
PubMed2001

Allosteric modification of oxygen delivery by hemoglobin.

UNLABELLED: Hemoglobin affinity for oxygen is altered by pH, temperature, and high altitude, making oxygen more readily available to the tissues. RSR13 (Allos Therapeutics, Denver, CO), an analog of the drugs clofibrate and bezofibrate, causes a dose-dependent, rightward shift of the oxygen dissociation curve in animals and humans. We tested the safety, pharmacodynamic, and pharmacokinetics of RSR13, an allosteric modifier of hemoglobin, in patients having general surgery in a prospective, randomized, double-blinded, placebo-controlled, dose-escalation clinical trial. After the induction of general anesthesia with endotracheal intubation, 26 patients who consented were randomly assigned to receive an infusion of RSR13 or placebo (2:1) in an ascending dose scheme. Doses studied were 10, 20, 30, 40, 50, 60, 75, and 100 mg/kg infused for 30--60 minutes. Samples were taken for determination of RSR13 concentration in plasma, red blood cells, and urine, as well as for determination of the p50 in blood by using three-point tonometry at frequent intervals after the infusion of the study drug. The RSR13 administration resulted in a dose-dependent rightward shift of the oxygen dissociation curve, with the target p50 shift of 10 mm Hg achieved at the 75- and 100-mg/kg doses. No differences were seen between RSR13 and placebo groups in laboratory or hemodynamic findings, with the exception of a transient, limited increase in serum creatinine in 3 patients who received RSR13. These increases peaked at 48 h (2.2, 3.5, and 4.5 mg/dL respectively), were not associated with oliguria, did not require treatment, and did not prolong hospitalization in any patient. The reasons for the unexplained increases in serum creatinine were not evident, but potentially included surgery itself (nephrectomy), patient condition, or the concomitant administration of renally cleared medications or drugs that affect renal blood flow. IMPLICATIONS: We studied the safety and tolerance of an investigational drug, RSR13 (Allos Therapeutics, Denver, CO), in general surgery patients. This drug, which increases the amount of oxygen available to the body, was well tolerated by the 17 patients who received it. There were clinically relevant increases in serum creatinine in 3 patients, indicating a decrease in renal function, but these increases were short-lived and resolved without treatment.

Adult↗
PubMed2001

Functional analysis of the leukemia protein ELL: evidence for a role in the regulation of cell growth and survival.

The ELL gene encodes an RNA polymerase II transcription factor that frequently undergoes translocation with the MLL gene in acute human myeloid leukemia. Here, we report that ELL can regulate cell proliferation and survival. In order to better understand the physiological role of the ELL protein, we have developed an ELL-inducible cell line. Cells expressing ELL were uniformly inhibited for growth by a loss of the G(1) population and an increase in the G(2)/M population. This decrease in cell growth is followed by the condensation of chromosomal DNA, activation of caspase 3, poly(ADP ribose) polymerase cleavage, and an increase in sub-G(1) population, which are all indicators of the process of programmed cell death. In support of the role of ELL in induction of cell death, expression of an ELL antisense RNA or addition of the caspase inhibitor ZVAD-fmk results in a reversal of ELL-mediated death. We have also demonstrated that the C-terminal domain of ELL, which is conserved among the ELL family of proteins that we have cloned (ELL, ELL2, and ELL3), is required for ELL's activity in the regulation of cell growth. These novel results indicate that ELL can regulate cell growth and survival and may explain how ELL translocations result in the development of human malignancies.

Amino Acid Chloromethyl Ketones↗
PubMed2001

Role of laryngoscopy, dual pH probe monitoring, and laryngeal mucosal biopsy in the diagnosis of pharyngoesophageal reflux.

There is no standard for determining significant pharyngoesophageal reflux. This prospective blind comparison study compared dual pH probe studies, direct laryngoscopy, and mucosal biopsy in children without symptoms of gastroesophageal reflux who underwent airway evaluation. Significant reflux to the lower esophageal probe did not correlate with statistical significance with reflux to the upper probe. In this group of asymptomatic patients, a positive lower pH probe finding did not correlate with upper or lower esophageal mucosal inflammation. Eosinophilia in the esophageal mucosa is diagnostic of gastroesophageal reflux disease, and was seen in 5 of the laryngeal biopsies. A weak correlation was seen between positive findings at laryngoscopy and positive posterior cricoid biopsy in this group. There may be no consistent way to predict significant pharyngoesophageal reflux in asymptomatic patients. Single-probe pH testing will not predict significant pharyngoesophageal reflux with mucosal changes. Laryngoscopy and upper pH probe findings only weakly correlate with significant histologic findings. Laryngeal and posterior cricoid biopsy may be the only sensitive test for mucosal injury. Clinical trials of empiric antireflux therapy should be used to determine whether the laryngeal changes seen in these patients are reversible.

Biopsy↗
PubMed2001

[Protective vegetal micronutrients and microcomponents for breast cancer].

This review is a summary of three reference books and of the final report of a European concerted action. The data have been updated by an analysis of recent publications, according to the same methodological criteria as those used in the reference books: sample size, quality of questionnaire and statistical methods. Mechanistic hypothesis are considered for each microcompounds, the effect of which is situated along the natural history of cancer. Few studies have considered folates effect on breast cancer, and they observed an interaction with the risk related to alcohol consumption, which is decreased with a high intake of folates. Many studies considered the effect of vitamin C and E, and carotenoids, but results are inconsistent. Conflicting results were also observed in studies on fibre and breast cancer. However, although only half of the studies showed a protective effect, the strength of the biological mechanisms give support to the hypothesis of a protection provided by fibre. The situation is comparable with phyto-estrogens: epidemiological studies are scarce and few of them show significant protection, but several plausible biological mechanisms are proposed, either related to the negative modulation of estrogen receptor by phyto-estrogen, or to the inhibition of proliferation by action on various enzymes. At the present time, caution in the interpretation of the results and in the use of plant microcompounds in prevention or therapy is strongly recommended.

Antioxidants↗
PubMed2000

Rescue of infectious classical swine fever and foot-and-mouth disease virus by RNA transfection and virus detection by RT-PCR after extended storage of samples in Trizol.

A method for storing samples containing classical swine fever virus (CSFV) or foot-and-mouth disease virus (FMDV), respectively, was developed, which abolishes the infectivity of both plus strand RNA viruses, and allows storage of samples above 0 degrees C for an extended time, yet preserves the viral RNA in a state which allows its detection by reverse transcription-polymerase chain reaction (RT-PCR), and even rescue of infectious virus after transfection of the extracted RNA into susceptible cells. Supernatants from infected cell cultures as well as organs from diseased animals were stored in Trizol(R) for 1-4 weeks at -20 degrees C, 4 degrees C, room temperature, or 37 degrees C. RNA was then extracted and used subsequently for RT-PCR, as well as transfection into susceptible cells to initiate the replication of progeny virus. Formaldehyde-fixed samples were also included in this study. Storage up to 4 weeks at 37 degrees C in Trizol(R) still yielded positive RT-PCR results and rescue of infectious virus upon RNA transfection. In contrast, formaldehyde fixation reduced drastically the detectability of viral RNA. This method represents a safe and inexpensive alternative to -70 degrees C (dry ice) storage or transport of samples, and abolishes the biosafety risks involved in shipping deep-frozen infectious materials.

Animals↗
PubMed2000

A comparison of dietary behaviour in Central England and a French Mediterranean region.

UNLABELLED: BJECTIVEe: The investigation involves comparison of dietary behaviour between UK and Mediterranean France by characterizing the pattern of the current French Mediterranean diet compared with the current British diet. DESIGN: The findings of two dietary surveys, one in the UK and one in France, are compared. An interviewer-administered questionnaire was used in both countries. Questions on food frequency were used to assess dietary behaviour, which were regrouped in the French survey to correspond with UK groupings. Dietary indices were constructed to describe dietary behaviour in relation to cancer recommendations for intake of fat, fibre, meat, fruit and vegetables. SETTING: The UK study was conducted in Leicestershire, central England and the French study was carried out in Hérault, southern France. SUBJECTS: UK: n=418 subjects (57.9% female and 42.1% male; mean age=45.0 y); France: n=635 subjects (50.1% female and 40.9% male; mean age=49.8 y). Age range of both samples: 20-74 y. RESULTS: There were positive and negative trends in food consumption in each country. UK respondents reported eating more beans and pulses (P=0.000), less cheese (P=0. 000), red meat (P=0.001), and processed meats (P=0.000) than French respondents. However, on the negative side, they ate less fruit and vegetables (P=0.000), fish and poultry (P=0.000), cereals (P=0.000), and more sweets and chocolates (P=0.000), and cakes, pastries, biscuits and puddings (P=0.000). Women had healthier diets in both countries. CONCLUSIONS: Overall the southern French diet was healthier as French respondents scored significantly better for indices for fat, dietary fibre, fruit and vegetables (P=0.000 in all cases). However, the French sample scored poorer for the meat index (P=0.000). SPONSORSHIP: This study was supported by a grant from l'Association de la Recherche contre le Cancer (ARC) awarded to M Holdsworth.

Adult↗
PubMed2000

Variation in the interaction between familial and reproductive factors on the risk of breast cancer according to age, menopausal status, and degree of familiality.

BACKGROUND: Studies have found that reproductive factors might have a variable effect on the occurrence of breast cancer (BC) according to the existence or not of a family history of BC. The effect of a family history of BC on the risk of BC may also vary according to the age at diagnosis and the degree of kinship. This may confound the relation between familial risk and reproductive factors. A combined analysis was performed to study the interaction between familial risk and reproductive factors according to degree of familiality, age at interview and menopausal status. METHODS: The present analysis included 2948 cases and 4170 controls in seven case-control studies from four countries. The combined relative risks were estimated using a Bayesian random-effects logistic regression model. RESULTS: The main effects of reproductive life factors on the risk of BC are in agreement with previous studies. Two-way interactions between subject's age or menopausal status and a family history of BC were not significant. Although the three-way interaction between age, familial risk and parity was not significant, familial risk seemed to be increased slightly for women with high parity compared with women with low parity in the older age group, and seemed to be slightly decreased for women with high parity compared with women with low parity in younger women. The subject's age also appeared to have an effect on the interaction between familial risk and the age at first childbirth (P = 0.1). CONCLUSIONS: A possible influence of reproductive and menstrual factors on familial risk of BC has been suggested previously and was also evident in the present study. Three-way interactions between age, family history and parity or age at first childbirth might exist and they merit further investigation.

Adult↗
PubMed2000

Validation of a food-frequency questionnaire using multiple-day records and biochemical markers: application of the triads method.

BACKGROUND: A food-frequency questionnaire (FFQ) used to assess usual food intake in Southern France has been validated by the classical means of multiple-day food records. To minimise over-estimation of the correlation between the dietary assessments by the FFQ and the reference method, which occurs if the random errors of questionnaire and reference measurement are positively correlated, a triangular comparison, the method of triads, was used. METHODS: We applied the triads model by comparing the FFQ with two multiple-day food records and three biomarkers. Only 87 subjects were included and completed the protocol. One biomarker (beta-carotene) was used for the 87 subjects and two biomarkers (urinary nitrogen and potassium) were measured in only 40 subjects. RESULTS: For beta-carotene intake assessment, the triad model, including the weighed multiple records (PETRA), was the best with estimates of validity coefficient of 0.39 [confidence interval (CI) 0.18-0.60] for the FFQ, 0.52 (CI 0.24-0.86), for PETRA and 0.85 (CI 0.43-1) for plasma levels of the nutrient. For protein and potassium intake assessment, the triad model including the estimated multiple records was the best only for the estimates of FFQ validity coefficient (0.61; CI 0.28-0.96 and 0.31; CI 0.09-0.66 respectively). CONCLUSION: Accuracy of the dietary assessment methods permitted a satisfactory estimation of the validity coefficient for beta-carotene intake by the FFQ, despite a small sample. However, the validity coefficients for protein and potassium showed wide CI values, indicating that a sample size < 50 subjects appears unsatisfactory for validation.

Adult↗
PubMed2000

[Nitrogen dioxide and ozone exposures in a population sample from Ile-de-France].

BACKGROUND: Individual exposure to NO(2)and O(3) has been estimated in an urban population sample in southern France and the determinants identified. The present study was conducted to evaluated individual exposure to NO(2) and O(3) and to identify the environmental determinants of exposure in a larger population living in different environmental conditions. METHODS: Two hundred ninety-four volunteers were recruited from the SUVIMAX sample in Ile-de-France. The study covered 2 periods of 5 consecutive days, one in winter and the other in the fall of 1998. Passive monitors were used to estimate individual exposure and indoor concentration at the participant's dwelling. Background atmosphere concentrations were obtained for the AIRPARIF surveillance network. Single and multiple ANOVA were used for statistical analysis. RESULTS: Individual exposures were low, especially for O(3) in the considered periods of time. Mean NO(2) and O(3)concentrations were 41 microg/m(3)/h and 16 microg/m(3)/h, respectively. The NO(2) individual exposure increased with the time spent in traffic and indoor concentration. The correlation coefficient between indoor and individual levels was r=0.73, and indoor concentration explained 50% of the variance in individual exposure. The site of the dwelling with regard to high traffic street, and most strongly, the presence of a gas stove influenced indoor concentration. However, mechanical air extraction decreased the mean indoor NO(2) level of the dwellings. CONCLUSION: This study allowed identification of the environmental determinants of NO(2) exposure in an urban sample. These data, together with those obtained previously, well be used to establish an exposure matrix for NO(2).

Air Pollutants↗
PubMed2000

[Appropriateness of antibiotic prescription in ENT surgery].

INTRODUCTION: Although extensive studies on the use of antibiotics during and after surgery exist, antibiotics are still used too liberally. PURPOSE: To analyse the appropriateness of antibiotic use in ENT surgery. PATIENTS AND METHODS: Retrospective study of all surgical procedures performed at the Department of Otolaryngology, Head and Neck Surgery of the University of Basel between April and June 1999. Of the 174 procedures 30 were classified clean, 50 clean-contaminated (group A), 69 clean-contaminated (group B), 14 contaminated, and 11 dirty. RESULTS: 9% of all patients received inappropriate antibiotic prophylaxis and 4% inappropriate primary antibiotic treatment. 22% of antibiotic prophylaxis, 39% of primary antibiotic treatments and 29% of secondary antibiotic treatments were considered inappropriate. DISCUSSION: The too liberal use of antibiotics during and after surgery is largely due to the surgeon's fear of infectious complications. Only a peer-review process of all antibiotic prescriptions can reduce the inappropriate use of antibiotics.

Antibiotic Prophylaxis↗
PubMed1999

Energy balance and cancers.

Energy balance results from the exact equilibrium between caloric intake and caloric expenditure. A caloric intake larger than caloric expenditure results in overweight, even obesity, but other determinants, like hormonal dysfunction and/or genetic traits may play a part in obesity syndrome. Obesity, and even overweight, have been recognized as risk factors for the development of cancers. Human epidemiological studies, which have tended to establish the nature of the relationship between energy balance and cancer, are summarized first, with the influence of the various factors which act both on obesity and on cancer risk. Among these factors are the macronutrients responsible for the caloric intake, and some lifestyle factors (physical activity, drinking habits and tobacco use). Second, the animal studies help to distinguish between different relevant factors, and to understand some of the underlying mechanisms. However, the insulin-resistance syndrome, which appears to underlie the relationship between obesity and hormone-dependent cancers, and possibly colon cancer, is only relevant to human physiology because hormonal alterations are part of it. Prevention of hyperinsulinemia, insulin resistance and the accompanying visceral obesity appears to be a major public health task for the prevention of cancers.

Animals↗
PubMed1999

Phase I trial to determine the safety, pharmacodynamics, and pharmacokinetics of RSR13, a novel radioenhancer, in newly diagnosed glioblastoma multiforme.

PURPOSE: To determine the safety, pharmacokinetics, and pharmacodynamic effect of 2-[4-(3, 5-dimethylanilino)carbonyl]methyl]phenoxy]-2-methylproprionic++ + acid (RSR13) 100 mg/kg/d with radiation therapy (RT) for glioblastoma multiforme (GBM). RSR13, a synthetic allosteric modifier of hemoglobin (HgB), is a novel radioenhancing agent that noncovalently binds to HgB, thereby reducing oxygen binding affinity and increasing tissue oxygen release to hypoxic tissues. PATIENTS AND METHODS: In this multi-institutional, dose frequency-seeking trial, 19 adult patients with newly diagnosed GBM received RSR13 100 mg/kg every other day or daily along with cranial RT (60 Gy/30 fractions). RSR13 was given over 1 hour by central venous access with 4 L/min of O(2 )by nasal cannula, followed by RT within 30 minutes. Pharmacokinetic (PK) and pharmacodynamic (PD) determinations were performed. The PD end point was shift in P50, the oxygen half-saturation pressure of HgB. RESULTS: Grade 3 dose-limiting toxicity occurred in none of the patients with every-other-day dosing and in two of the 10 patients with daily dosing. Grade 2 or greater toxicity occurred in three out of nine and six out of 10, respectively. PK and PD data demonstrate that a substantial PD effect was reliably achieved, that PD effect was related to RBC RSR13 concentration, and that there was no significant drug accumulation even with daily dosing. The mean shift in P50 was 9.24 +/- 2.6 mmHg (a 34% increase from baseline), which indicates a substantial increase in tendency toward oxygen unloading. CONCLUSION: Daily RSR13 (100 mg/kg) during cranial RT is well tolerated and achieves the desired PD end point. A phase II trial of daily RSR13 for newly diagnosed malignant glioma is currently accruing patients within the New Approaches to Brain Tumor Therapy Central Nervous System Consortium to determine survival outcome.

Adult↗
PubMed1998

Typhoid fever in the United States, 1985-1994: changing risks of international travel and increasing antimicrobial resistance.

BACKGROUND: Typhoid fever is a potentially fatal illness common in the less industrialized world. In the United States, the majority of cases occur in travelers to other countries. METHODS: We reviewed surveillance forms submitted to the Centers for Disease Control and Prevention, Atlanta, Ga, for patients with culture-confirmed typhoid fever between 1985 and 1994. RESULTS: The Centers for Disease Control and Prevention received report forms for 2445 cases of typhoid fever. Median age of patients was 24 years (range, 0-89 years). Ten (0.4%) died. Seventy-two percent reported international travel within the 30 days before onset of illness. Six countries accounted for 80% of cases: Mexico (28%), India (25%), the Philippines (10%), Pakistan (8%), El Salvador (5%), and Haiti (4%). The percentage of cases associated with visiting Mexico decreased from 46% in 1985 to 23% in 1994, while the percentage of cases associated with visiting the Indian subcontinent increased from 25% in 1985 to 37% in 1994. The incidence of typhoid fever in US citizens traveling to the Indian subcontinent was at least 18 times higher than for any other geographic region. Complete data on antimicrobial susceptibility to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole were reported for 330 (13%) Salmonella Typhi isolates. Isolates from 1990 to 1994 were more likely than isolates from 1985 to 1989 to be resistant to any of these antimicrobial agents (30% vs 12%; P<.001) and to be resistant to all 3 agents (12% vs 0.6%; P<.001). CONCLUSIONS: American travelers to less industrialized countries, especially those traveling to the Indian subcontinent, continue to be at risk for typhoid fever. Antimicrobial resistance has increased, and a quinolone or third-generation cephalosporin may be the best choice for empirical treatment of typhoid fever.

Adolescent↗