Factors influencing the incidence and prevalence of food allergy.

Food allergy is an increasing problem in Europe and elsewhere and severe reactions to food are also becoming more common. As food allergy is usually associated with other forms of allergic sensitisation it is likely that many risk factors are common to all forms of allergy. However the potential severity of the disease and the specific public heath measures required for food allergy make it important to identify the specific risk factors for this condition. Food allergy is unusual in that it often manifests itself very early in life and commonly remits with the development of tolerance. Hypotheses that explain the distribution of food allergy include specific genetic polymorphisms, the nature of the allergens involved and the unique exposure to large quantities of allergen through the gut. Progress has been made in developing more specific and testable hypotheses but the evidence for any of these is still only preliminary. Further collaborative research is required to develop an appropriate public health response to this growing problem.

Probiotic research in Australia, New Zealand and the Asia-Pacific region.

Although the epicentres of probiotic research in the past decade have been Japan and Europe, researchers in the Asia-Pacific region have actively contributed to the growing understanding of the intestinal microbial ecosystem, and interactions between gut bacteria, diet and health of the human host. A number of new probiotic strains have been developed in the region that have been demonstrated to have beneficial impacts on health in animal and human trials, including improved protection against intestinal pathogens and modulation of the immune system. Probiotics targeted to animals, including aquaculture, feature heavily in many Asian countries. Developments in probiotic technologies have included microencapsulation techniques, antimicrobial production in fermented meats, and synbiotic combinations. In particular, the impact of resistant starch on the intestinal environment and fermentation by intestinal bacteria has been intensively studied and new probiotic strains selected specifically for synbiotic combinations with resistant starch. This paper provides an overview of probiotic research within Australia, New Zealand and a number of Asian countries, and lists scientists in the Asia-Pacific region involved in various aspects of probiotic research and development.

Stem cell transplantation in the normal nonmyeloablated host: relationship between cell dose, schedule, and engraftment.

In previous studies we have shown high rates of stable engraftment when 40 million male BALB/c cells were infused intravenously daily for 5 days (a total of 200 million cells) to normal nonmyeloablated female hosts. The present studies evaluate engraftment of male BALB/c bone marrow cells in female host marrow, spleen, and thymus 20-25 weeks after transplantation using varying cell dosages within a 5-day schedule. Engraftment in recipient mice was assessed by detection of male specific sequence in recipient DNA from each organ. When 40 million cells were given per daily injection for 1, 2, 3, 4, or 5 days, engraftment percentages in host marrow were 11 +/- 0.83, 20 +/- 2.0, 23 +/- 2.5, 32 +/- 6.3, and 39% +/- 5.7 (+/- standard error of mean), respectively, yielding engraftment percentages per million cells infused of 0.28, 0.25, 0.19, 0.20, and 0.20%, respectively. When levels of 2.5, 5, 10, 20, or 40 million cells were injected 5 times over a 5-day schedule into normal BALB/c female hosts, progressively increasing levels of engraftment from 3 +/- 0.6 to 39% +/- 5.7 were seen in host marrow. Highest levels of engraftment per million cells injected were obtained on days 1 and 2 of a 5-day schedule and with a level of 10 million cells given daily over 5 days. Engraftment profiles varied with spleen and thymus and percent engraftment was generally lower than for marrow. The present work indicates that regardless of cell level infused or number of infusions, rates of engraftment observed in marrow approached or exceeded the highest rates of engraftment estimated by theoretical calculations based on replacing host cells ("replacement model") or adding to host cells ("incremental model"). Engraftment in spleen and thymus was lower, but also at times approached or exceeded theoretical maxima. These data show extraordinary levels of engraftment in normal hosts, suggesting that rates in this competitive model are superior to those seen in irradiated hosts; alternatively, there may be selective repression of host stem cell proliferation and differentiation.

Cytokine expression from bone marrow derived macrophages.

Monocytes and macrophages show marked phenotypic variation dependent on their tissue of origin. Peripheral blood monocytes have been found to be sources of a variety of cytokines, but isolated marrow macrophages have not been characterized in this regard. Marrow macrophages form a predominant component of murine adherent Dexter stromal cells and can be isolated by sequential explant culture in colony-stimulating factor-1 (CSF-1). We have studied murine (Balb/c) bone marrow macrophage (BMM) cytokine production in the presence or absence of CSF-1, the lectin pokeweed mitogen (PWM) or interleukin-3 (IL-3). Biologic activity in conditioned media (cm) from control and induced BMM was assessed using the factor-dependent cell lines 32D, NFS-60, T1165, MC-6 and FDC-P1. Cell line stimulation and antibody blocking indicated the presence of c-kit ligand, interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF). This stimulatory activity was increased by exposure to PWM or the combination of CSF-1 and PWM or CSF-1 and IL-3. CSF-1, as determined by radioimmunoassay (RIA), was essentially undetectable in baseline cm and induction was not seen with PWM or CSF-1. Baseline or "constitutive" expression of BMM and mRNA for CSF-1 and c-kit ligand was seen. Uninduced BMM did not express mRNA for G-CSF, granulocyte-macrophage CSF (GM-CSF), IL-6 or IL-3. CSF-1 induced increased expression of IL-6 mRNA, PWM induced increased expression of G-CSF and IL-6 mRNA and the combination of PWM and CSF-1 induced expression of CSF-1, G-CSF and IL-6 mRNA. Varying levels of CSF-1 had differential effects on cytokine production. Increasing levels of CSF-1 increased IL-6 mRNA and downmodulated CSF-1 mRNA expression. There was a biphasic response of c-kit ligand mRNA expression to CSF-1 exposure; low levels of CSF-1 (50 U/mL) induced, while higher levels (2000 U/mL) inhibited, expression. These data indicate that BMM (and by analogy the macrophage component of Dexter culture stroma), are important sources of CSF-1 and c-kit ligand but not GM-CSF or IL-3. BMM can also be induced to express IL-6 and/or G-CSF. Lastly, CSF-1, by differentially modulating BMM cytokine production in a holocrine or autocrine manner, may function as a central regulator of stromal based hematopoiesis.

Quality assurance criteria for probiotic bacteria.

Acid and bile stability and intestinal mucosal adhesion properties are among the criteria used to select probiotic microbes. The quality control of probiotic cultures in foods traditionally has relied solely on tests to ensure that an adequate number of viable bacteria are present in the products throughout their shelf lives. Viability is an important factor, but not the only criterion for quality assurance. To be effective, probiotic strains must retain the functional health characteristics for which they were originally selected. Such characteristics include the ability to survive transit through the stomach and small intestine and to colonize the human gastrointestinal tract. In vitro test protocols can be readily adopted to examine the maintenance of a strain's ability to tolerate acidic conditions, survive and grow in the presence of bile, and metabolize selective substrates. Molecular techniques are also available to examine strain stability. Adhesion characterization may be an important quality-control method for assessing gut barrier effects. Adhesion has been related to shortening the duration of diarrhea, immunogenic effects, competitive exclusion, and other health effects. Adhesion properties should be carefully monitored, including adhesion to intestinal cells (eg, Caco-2) and human intestinal mucus. This article outlines the types of in vitro testing that can be used to ensure quality control of functional probiotic strains.

Determination of net ionic charge on Tc-99m DTPA and Tc-99m EDTA by a column ion-exchange method.

The net charge on a stable complex ion is conveniently measured at tracer levels by studies of ion-exchange equilibrium. Previous applications to radiopharmaceuticals have used a batch equilibrium method, but such measurements are affected by any radiochemical impurities present. Since technetium pharmaceuticals are often heterogeneous, it is of value to have a technique that is directly applicable to a mixture of different species. Such a method is presented here: a column method to determine the net charge on the technetium-99m complex of diethylenetriaminepenta-acetic acid (DTPA), and also on the principal component in a mixture of species formed by reducing pertechnetate in the presence of ethylenediaminetetra-acetic acid (EDTA). The net charge was calculated from the effect of eluent concentration on retention time. The net charge on Tc-DTPA was found to be -2 at both pH 4.6 and 7.0. The net charge on the Tc-EDTA complex, measured at pH 7.0 only, was also -2.

Surveying graduates of one school to determine regional workforce demand.

PURPOSE: To study the demand for physician graduates from one school in one region of the country. The use of demand as a measure of potential regional variation should be of interest to medical educators and policymakers. METHOD: All residency graduates of the University of Washington School of Medicine between 1975 and 1995 (n = 3,824) were surveyed about their ability to gain employment in a timely manner and whether they were recruiting physicians for their practices. RESULTS: The response rate was 50.29%. A non-responder survey was done using a subsample (n = 200), with a 28% return. Over 95% of the graduates had found employment in their desired specialties and locations within two years of finishing their residencies. This was the same for graduates over all years. Approximately 30% of all practices of respondents within the Northwest region were recruiting for new physicians (26% of specialty practices and 34% of generalist practices were recruiting). There was no difference between recruitment in the urban and rural practices or between respondents to the initial survey and those responding to the follow up. CONCLUSIONS: Despite a significant oversupply of specialist physicians and at least a sufficient supply of generalist physicians nationally, there appears to be a strong demand for both specialists and generalists in the Northwest region of the country. This raises questions concerning the use of national averages to inform the education policies in specific regions of the country. More validated measures of demand are needed for future studies.

Synthesis and utilisation of folate by yoghurt starter cultures and probiotic bacteria.

Thirty-two bacterial isolates from species commonly used in yoghurts and fermented milks were examined for their ability to synthesise or utilise folate during fermentation of skim milk. The organisms examined included the traditional yoghurt starter cultures, Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus, and probiotic lactobacilli, bifidobacteria, and Enterococcus faecium. Folate was synthesised by S. thermophilus, bifidobacteria, and E. faecium. S. thermophilus was the dominant producer, elevating folate levels in skim milk from 11.5 ng g(-1) to between 40 and 50 ng g(-1). Generally, lactobacilli depleted the available folate in the skim milk. Fermentations with mixed cultures showed that folate production and utilisation by the cultures was additive. Fermentations using a combination of Bifidobacterium animalis and S. thermophilus resulted in a six-fold increase in folate concentration. Although increased folate levels in yoghurts and fermented milks are possible through judicious selection of inoculum species, the folate levels remain relatively low in terms of recommended daily allowance.

Gut bacteria and health foods--the European perspective.

Probiotics, prebiotics, and synbiotics aimed at improving intestinal health currently represent the largest segment of the functional foods market in Europe, Japan and Australia. Evidence continues to emerge demonstrating that these ingredients have the potential to improve human health in specific intestinal disorders. The European Commission, through its 5th Framework Programme, is presently focusing on a substantial effort in the science of the intestinal microbiota, its interaction with its host and methods to manipulate its composition and activity for the improvement of human health and well being. Eight multicentre and multidisciplinary research projects now cover a range of topics required for the development of efficacious probiotic foods, from understanding probiotic mechanisms at a molecular level; developing technologies to ensure delivery of stable products; and demonstrating safety and efficacy of specific probiotics in defined treatment targets. This concerted research effort promises to provide us with an enhanced understanding of the human intestinal microbiota's role in health and disease, and new approaches and products to tackle a variety of intestinal problems.

The Balanced Budget Act of 1997 and rural training supported by Medicare graduate medical education funds.

The Balanced Budget Act of 1997 promised a number of changes in medical education to benefit rural communities. The changes suggested that physician training would be more available in rural communities, programs training physicians for work in rural communities would be better supported, and residency programs would be allowed to be separate from hospitals. The regulations developed by the Health Care Financing Administration to implement the act are reviewed in the context of these expectations. Limitations in the regulations indicate that rural communities will see little benefit from this legislation. This article is a commentary on the expectations and reality of the effects of the Balanced Budget Act of 1997 on rural training supported by Medicare.

The effects of payback and loan repayment programs on medical student career plans.

Many states have considered implementing payback programs on state-subsidized medical education to increase the rate of graduates returning to those states to practice. An alternative is for states to offer and expand loan repayment programs to entice medical school graduates from rural states to return to their home states. The goal of this study is to determine and contrast the impact these two types of programs might have on medical school choice and students' intentions to return to their home states. Two hundred twenty-nine medical students were surveyed (response rate 80 percent). The questionnaire collected background information on the students and addressed the possible impact of payback and loan repayment policy proposals on student plans. Forty-seven percent of students reported that they would attend a different medical school if a required payback program were in place. Students who were more competitive at the time of admission to medical school were significantly more likely to say they would attend another medical school than were less competitive students. In contrast, 48 percent of students reported that they would be more likely to return to their home states if expanded loan repayment programs were available for service in areas of need. The findings suggest that payback programs may dissuade more competitive students from entering medical schools with such requirements, compromising the pool of students most likely to return to rural areas. Conversely, medical students appear willing to consider loan repayment programs upon completion of their training.

An expert panel approach to assessing the rural implications of health care reform: the case of the Health Security Act.

The policy arena is hungry for objective information regarding the potential effects of comprehensive national and state health care reform. Such information reduces the dependence of policy-makers on information generated solely by advocacy groups and serves as a checkpoint for such information. Unfortunately, the academic community is often unable to mobilize its resources quickly enough to help meet this information need. This article describes one model for overcoming this difficulty. When the time frame is especially short, academic expertise can be brought together in the form of an expert panel. However, for such an approach to be effective, it must be carefully configured and orchestrated. Critical ingredients include much preparatory groundwork, a well-defined framework and methodology for conducting the policy analysis, and a professional facilitator. The Rural Policy Research Institute used such an approach to analyze President Clinton's Health Security Act shortly after the initial blueprint was released (but before the legislative language was released). The consensus of the expert panel was that the Health Security Act would, on balance, represent an improvement over today's rural reality. However, a number of troubling aspects were noted. First, the Act's emphasis on primary care and nonphysician providers is a double-edged sword. While these are precisely the types of providers needed in rural areas, the short-run effect may be to create increased competition for such providers from urban areas.(ABSTRACT TRUNCATED AT 250 WORDS)