Large Number Of Healthy Individuals Research Articles

Reference Intervals (RIs) in veterinary medicine

Reference Intervals (RIs) are necessary in veterinary clinical pathology to provide a data base in order to compare results obtained from healthy versus diseased animals. Data are obtained from laboratory tests and, depending on whether they have a Gaussian or non-Gaussian distribution, are processed through statistical tests to define the RIs. This process begins with a healthy reference population made up of individuals who have been initially chosen based on inclusion or exclusion criteria. It is frequently challenging to have a large number of healthy individuals on which to establish de novo RIs, especially in wild and exotic animals. However, the use of reference intervals in daily clinical practice remains a fundamental instrument for therapeutic and diagnostic decisions, but it must always be accompanied by clinical findings that can confirm the hypothesis.

Continuous age- and sex-specific reference ranges of liver enzymes in Chinese children and application in pediatric non-alcoholic fatty liver disease.

Alanine aminotransferase (ALT) is widely used to screen patients with hepatic diseases. However, the current reference ranges (< 50 U/L) were developed by laboratories and have not been validated in populations with a large number of healthy individuals. This study collected venous blood and anthropometric data from a total of 13,287 healthy children aged 3months to 18years who underwent routine physical examinations in the Department of Pediatric Healthcare. We applied the least mean square algorithm to establish age- and sex-related reference percentiles of serum levels of transaminases. For validation, we recruited 4276 children and adolescents with obesity/overweight who underwent evaluation and metabolic tests in the hospital. Using receiver operating characteristic curves, we determined age- and sex-specific upper limit percentiles of liver enzymes for fatty liver diseases. This study revealed a significant correlation between serum transaminase levels and age and sex (P < 0.01). These transaminase levels exhibited age- and sex-specific patterns. Among individuals in the non-alcoholic fatty liver disease (NAFLD) cohort, elevated ALT levels displayed a positive association with clinical markers of disease severity, including homeostatic model assessment of insulin resistance, waist-hip ratio, and serum uric acid levels (P < 0.01). According to the receiver operating characteristic curves, ALT levels at the 92.58th percentile for boys and the 92.07th percentile for girls yielded the highest accuracy and specificity. This study provides age- and sex-specific reference ranges for ALT, aspartate aminotransferase, and γ-glutamyltransferase in Chinese children and adolescents, making it the largest population study to date. Furthermore, the study establishes a precise upper limit for ALT levels, facilitating their use in NAFLD screening. Video Abstract.

P097 Epidemiology of dermatophytes related infections in Kuwait: a retrospective study

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Introduction and ObjectiveDermatophytes are a common cause of cutaneous infections that affect a large number of healthy individuals throughout their lives. Although such infections are classically benign, they have a negative impact on patient’s physical and psychological health. We aim to explore the epidemiology of dermatophytes infections at a national level.MethodsThe study was conducted retrospectively. Demographic and microbiological data were obtained from laboratory information system in the Mycology Reference Laboratory in the year 2021. Dermatophytes were either isolated from clinical samples in mycology reference laboratory or sent from other laboratories for species identification. The clinical samples were divided into two parts. The first half was examined microscopically, and the second half was inoculated on Sabouraud agar media with and without cycloheximide and then incubated at 30°C for at least 2 weeks. Dermatophytes were identified by colonial morphology and microscopic characteristics.ResultsDuring the year 2021, 60 dermatophytes were found. The male to female ratio was 2:1. A total of 60% of patients were children. Half of the cases were isolated from hair specimens and the second half were from the skin. Only one dermatophyte was isolated from nail cultures. Regarding dermatophytes distribution, Microsporum species were the commonest and involved mostly M. canis (26). Other less common species included two M. audouinii and two M. praecox. A total of seven other Microsporum species were not identified to species level. On the other hand, 23 Trichophyton species were found including 5 T. tonsurans, 4 T. interdigitale, 3 T. rubrum, 1 T. simii, and 1 T. erinacei. A total of 9 other Trichophyton species were not identified to species level.ConclusionsHigher rates of infection were seen in males compared to females. Phenotypic identification has failed in identifying a significant number of isolates. As in other types of molds, the phenotypic examination may also result in inaccurate identification, especially among uncommon and evolving species. Hence, molecular testing is essential for accurate identification and better understanding of the epidemiology of dermatophytes-related infections. The following species were reported for the first time in Kuwait, namely: T. erinaceid, T. simii, and M. praecox.

Gender-dependent frequency of unconventional T cells in a healthy adult Caucasian population: A combinational study of invariant NKT cells, γδ T cells, and mucosa-associated invariant T cells.

This study tested the hypothesis of gender bias in frequency of unconventional T cells. Unconventional T cells exist as minor subsets of T cells in peripheral blood. Despite their low number, they play a crucial role in various immune-mediated diseases such as inflammation, autoimmunity, allergy, and cancer. Gender-based frequency of these cells altogether on large number of healthy individuals are unestablished creating hurdles to manifest association with various immune-mediated pathologic conditions. In this study, we used a multicolor flow cytometric panel to identify iNKT cells, γδ T cells, and MAIT cells altogether in the peripheral blood samples of 93 healthy adult males and 109 healthy adult females from the Caucasian population. The results revealed iNKT cell median value (% T cells) in females was higher: 0.114% ranging from 0.011 to 3.84%, than males: 0.076% (p value 0.0292), ranging from 0.007 to 0.816% and found to be negatively correlated with age in females (p value 0.0047). However, γδ T cell median value in males was higher: 2.52% ranging from 0.31 to 16.09%, than females: 1.79% (p value 0.0155), ranging from 0.078 to 12.49% and each gender was negatively correlated with age (male p value 0.0003 and female p value 0.0007). MAIT cell median values were 3.04% ranging from 0.11 to 10.75% in males and 2.67% ranging from 0.2 to 18.36% in females. MAIT cells did not show any statistically significant difference between genders and found to be negatively correlated with age (p value<0.0001). Our results could be used for further gender-wise investigations of various pathologic conditions such as cancer and their prognosis, autoimmune diseases, allergies, and their pathogenicity.

Helicobacter Pylori IgG Sero-Prevalence Study in Two Adjacent Regions of Contrasting Gastric Cancer Rates and Bracken Fern Frequency in Western Venezuela

As Human Gastric Cancer Death Rates (HGCDR) is unevenly distributed in western Venezuela, we explored possible risk factors, among which Helicobacter Pylori (Hp) infection alongside bracken fern invasion could be differential contributors. A prospective transversal study for Hp seroprevalence was conducted in a large number of healthy individuals (15-65 years) in two geographically distinct zones (low megathermic and mountain mesothermic, 0-3000 meters) employing IgG Hp ELISA response at district level.

A study of adverse vaccine events among pediatric age group in a tertiary medical college hospital

Background: Vaccines are pivotal health products that are used and administered prophylactically to a large number of healthy individuals. A significant proportion of vaccines are administered to the pediatric age group, particularly to the neonates and infants as part of the national immunization programmes. As with any drug, untoward reaction can occur with the administration of vaccines. Most of the clinical trials with the vaccines are conducted and validated in a relatively small sample size. Active monitoring as part of the Pharmacovigilance programme is imperative to identify rare or deferred adverse vaccine events (AVE). Methods: A prospective, single center, observational, naturalistic study on report forms in pediatric age group, who may develop AVE in Sapthagiri Institute of Medical Sciences and Research Center, Bengaluru, was conducted during the study time widow, from February 20, 2014, to April 20th, 2014. Children under 5 years of age were included in the study. All children more than 5 years of age were excluded from the study. The causality assessment were attempted to be recorded as per the Naranjo score, which is used to quantitatively evaluate the association between AVE and vaccines. Results: 19.04% of children aged 1-5 years of age documented with adverse event following immunization (AEFI) (p=0.036). It was found that either a naive or the fully immunized children suffered from the AEFI most of which was trivial. Fever was the most common AEFI reported followed by an excess cry. The incidence of fever reported was substantially high following the DPT vaccine. Conclusions: All the AEFI received through the telephonic calls were documented. There was no mortality or a major adverse event reported. Maximum AEFI were documented in the neonates and the children 1-5 years of age which was statistically significant. In addition, the study provides a scope for further research with reference to the inter-age group variability. The immune mechanism behind such a difference also needs to be explored.

Comparative analysis of the 1-mile run test evaluation formulae: Assessment of aerobic capacity in male law enforcement officers aged 20–23 years

The purpose of this study was to compare values of aerobic performance in the 1-mile run test (1-MRT) using different formulae. Aerobic capacities of 351 male volunteers working for the Turkish National Police within the age range of 20-23 years were evaluated by the 1-MRT and the 20-metre shuttle run (20-MST). VO2max values were estimated by the prediction equations developed by George et al. (1993), Cureton et al. (1995) and Kline et al. (1987) for the 1-MRT and by Leger and Lambert (1982) for the 20-MST. The difference between the results of the different formulae was significant (p = 0.000). The correlation coefficient between the estimated VO2max using Cureton's equation, George's equation, Kline's equation and the 20-MST were 0.691 (p < 0.001), 0.486 (p < 0.001) and 0.608 (p < 0.001), respectively. The highest correlation coefficient was between the VO2max estimated by the 20-MST and Cureton's equation. Similarly, the highest correlation coefficient (r = -0.779) was between the 1-mile run time and the VO2max estimated by Cureton's equation. When analysing more vigorous exercise than sub-maximal exercise, we suggest that Cureton's equation be used to predict the VO2max from 1-mile run/walk performance in large numbers of healthy individuals with high VO2max. This research compares the use of 3 different formulae to estimate VO2max from 1-mile run/walk performance in male law enforcement officers aged 20-23 years for the first time and reports the most accurate formula to use when evaluating aerobic capacities of large numbers of healthy individuals.

A stable panel comprising 18 urinary proteins in the human healthy population

Just as biomarkers specific for diseases, biomarkers indicative of healthy conditions are valuable for the early diagnosis, monitoring, and prognosis of diseases. Our study focused on discovering via proteomics a stable panel of urinary proteins in the human healthy population. Urine samples were collected three times during 4 months from 100 male and 100 female healthy donors and analyzed through four different fractionation techniques (i.e. in-gel, 2D-LC, OFFGEL, and mRP) coupled with HPLC-Chip-MS/MS. Thus, 1641 urinary proteins were identified with a high confidence, among which 70 exhibiting an intergender/day variation <0.25 were selected and matched with the previously published five largest urinary proteomes to get 56 candidate proteins. Next, a panel comprising 18 intact urinary proteins was constructed by comparing the urinary proteomes via SDS-PAGE and 2DE. Finally, such 18 urinary proteins were validated via enzyme-linked immunosorbent assay in eight healthy individuals. Most of these proteins had been related to multiple rather than to single diseases. Therefore, we surmise that this protein set could be used as a biomarker to assess the human health status. Further determinations of the normal fluctuations of the single urinary proteins in this series using samples from large numbers of healthy individuals are required prior to any application in clinical settings.

Subject‐based reference values: biological variation, individuality, and reference change values

Subject-based reference values have been largely overlooked in veterinary medicine. These values represent longitudinal data rather than the cross-sectional data represented by standard population-based reference values. As such they provide information about biological and analytical variation. Inherent random variation of analytes around a homeostatic set point is referred to as biological variation; data on biological variation are underutilized in veterinary medicine and have multiple applications that include setting analytical goals, predicting the utility of population-based reference intervals (RIs), assessing the value of partitioning reference values, and evaluating the significance of changes in serial results. To generate these data, relatively few individuals are sampled for a short period of time. Given the difficulty of obtaining specimens from large number of healthy individuals to establish a cross-sectional RI for many veterinary species, especially exotic species, use of subject-based RIs is a practical alternative approach for the veterinary diagnostician. Furthermore, for the majority of biochemical analytes and even many hemostatic variables, population-based reference values are less sensitive than subject-based reference values for detecting pathologic changes in an individual. The focus of this review is the clinical usefulness of subject-based reference values and diagnostic implications for their use. Implementation of the concepts of biological variation, individuality, and reference change value (RCV) may allow large diagnostic laboratories to offer more sensitive reference values to assess health and detect disease.

Disease-relevant autoantibodies in first episode schizophrenia

Disease-relevant autoantibodies in first episode schizophrenia

Community Engagement in Diverse Populations for Alzheimer's Disease Prevention Trials

Background: Among the impediments to Alzheimer’s disease (AD) primary prevention trials is a general difficulty identifying large numbers of healthy individuals willing to participate in extended treatment studies. The individuals responding to studies typically do not include large numbers of African-Americans (AfAms), a group at high risk for AD but also historically reluctant to participate in medical research. Objective: The present study was designed to develop a research-ready registry of normal community volunteers, 55 years of age or older, who are willing to participate in AD prevention studies. A focus of this "Alzheimer's Disease Prevention Registry (ADPR)" was to engage AfAms in research. Methods: Project planning was coordinated through the Joseph and Kathleen Bryan ADRC African American Community Outreach Program, a trusted program established in 1995 to disseminate AD information to underserved AfAm communities across the state of North Carolina. The ADPR recruitment relied on established community partnerships and personal contacts through weekly events, such as health fairs and educational venues at medical centers, senior housing facilities, and churches. A key emphasis was on community ownership in medical research that advances local needs. Registration could be done either by completing response cards, by telephone, or through accessing a secured website. Participants were allowed to opt in or out of studies depending on their interest (e.g. imaging/biomarkers, pharmacological interventions, nonpharmacological interventions). Results: In the first 4 months of the registration effort, over 410 individuals have enrolled. Of these nearly 40% (n=163) are AfAms. The majority have expressed interest in participating in all types of studies (66%); whereas, a small group (17%) have specifically declined participation in pharmaceutical trials. Others have expressed specific interest in limited areas, such as imaging studies (3%) or nonpharmacological studies (14%). Conclusions: It is possible to quickly assemble research registries that target those most likely to participate in future prevention studies and also include large numbers of AfAms, typically underrepresented in research. If registries similar to our ADPR were implemented across other national AD centers, prevention studies could be facilely initiated, speeding the development of therapies in representative populations and avoiding the need of expensive, inefficient recruitment campaigns. Author Disclosure Information: K.A. Welsh-Bohmer, None; H.L. Edmonds, None; M.I. McCart, None; K.M. Hayden, None; H.R. Romero, None; J.N. Browndyke, None; L.P. Gwyther, None; J.R. Burke, None. Presentation Preference (Complete): Poster Topic (Complete): Prevention Learning Objectives (Complete): Verb: describe Learning Objective: : major impediments to primary prevention trials Verb: identify Learning Objective: : specific obstacles and barriers impeding participation of African Americans Verb: summarize Learning Objective: : procedures to engage community in a research ready registry for prevention studies

Is There a Role for New Invertebrate Models for Aging Research?

OUR current major invertebrate models for research on the biology of aging, the worm, Caenorhabditis elegans, and the fruit fly, Drosophila melanogaster, have been, and will continue to be, major sources of insight for the field. However, these models have certain shortcomings that make the development of additional invertebrate models worthwhile. Foremost among these shortcomings is that worms and flies belong to the same superphylum, the Ecdysozoa, and both species have undergone extensive gene loss since their divergence from their common ancestor with humans (Figure 1). This is clearly shown by the discovery that more than 10% of the genes identified in a more distantly related phylum, the Cnidaria, have clear human homologs, which are not found in worm or fly genomes (1). Thus, there remains a substantial genomic universe of potential relevance to humans that has not yet been screened for longevity genes. Both the Cnidaria and the Lophotrochozoa, which also share unique genetic orthologues with humans, offer potentially rewarding model species. Second, worms and flies both have limited (or no) somatic cell division in adulthood and have virtually no regenerative potential. Third, both worms and flies use special nonaging life history stages in times of environmental stress (dauer in worms, reproductive diapause in flies), which may be partially induced by genetic or environmental manipulations that extend life (2,3). Humans have no apparent equivalent of these stages, and it would be unfortunate if successes in extending life in these model species were due to a phenomenon not reproducible in humans. Additional invertebrate models with proliferating cells in the adult as well as extensive regenerative potential might be informative for learning how to manage the perils of lifelong cell division, coupled with the potential for tissue regeneration. Figure 1. The major groups of multicellular animals (yeast and protozoa as out-group). Note that genetic screening for longevity mutants has not yet been performed for any Cnidarian or Lophotrochozoan species, although they share with humans orthologous genes that ... To be most useful in screening for new genes, prospective new invertebrate models would ideally possess three features: (i) the ability to be mass cultured in the laboratory, (ii) reasonably short life span, and (iii) tractable genetics. It is important that large numbers of healthy individuals can be produced and maintained, so that life span studies of a large number of mutants is possible. Other things being equal, the shorter the life span, the better, although as with any aging study, it is important that the animals in the study be healthy, that is, not short lived because their laboratory husbandry is so poor that they are unhealthy throughout their short lives. Finally, tractable genetics makes mutant screening possible and implies that manipulation of gene expression will be reasonably straightforward. Clearly, species that combine all these features at present would likely already be used extensively in aging research, so we focused our attention on species that appear to possess two of the three (mass culturing, short life span), with indications that tractable genetics might be fairly easily developed. Given this background, we believe that the following animals bear consideration for development as new invertebrate models for aging research.

Gene expression profiling in blood: new diagnostics in alcoholism and addiction?

The successful treatment of most diseases relies heavily upon early detection. Biomarkers with diagnostic and prognostic value are critical to the addiction field. Most individuals with alcohol or drug dependence or use problems evade detection until severe medical, legal, or social consequences arise. The short half-life of alcohol in the blood after cessation of drinking eliminates the feasibility for using blood alcohol as a biomarker. Carbohydrate-deficient transferrin (CDT) is currently the most specific serum marker of chronic, heavy alcohol use (Reynaud et al, 2000), but the low sensitivity of the CDT test in the general population makes it an unreliable candidate for predicting either heavy alcohol use or for diagnosing alcohol abuse and/or dependence (Alte et al, 2004). Except for the drugs and their metabolites, there are not biomarkers for addiction. Advances in the field of genomics offer new diagnostic and screening potential for complex genetic diseases like addiction. The ability to simultaneously measure the level of all possible transcripts (mRNAs) provides an unbiased view of potential biomarkers. The importance of understanding gene expression changes in alcohol and drug dependence can be appreciated by the impact of expression profiling in other diseases, most notably cancer, where studies have led to improved pharmacotherapies and to a molecular classification of disease. Gene expression profiling is only beginning to be applied to psychiatric illnesses and may also provide an accurate means to diagnose these conditions. Human brain gene expression studies of alcoholics and cocaine abusers suggest that specific patterns of gene expression may underlie addiction-related phenotypes and provides evidence that a molecular classification of alcoholism may be feasible in the future (Liu et al, 2006; Mash et al, 2007). However, in order for expression profiling to be useful in the clinical screening of dependence and consumption, the tissues or cells under investigation need to be readily accessible. A wide variety of screening tests are available that relies upon peripheral blood samples for assaying biological markers. For example, blood tests allow early detection, and in some cases prevention, of conditions such as prostate cancer, diabetes, thyroid dysfunction, and heart disease. Blood samples offer advantages over procedures such as tissue biopsy as they are fast, noninvasive, and can be repeated many times on the same individual. Blood biomarkers also offer the potential to predict disease before any detrimental symptoms are manifested. Genomic profiling of peripheral blood samples could be of great value in identifying biomarkers for complex diseases including addiction. This idea is supported by studies utilizing white blood cells to identify discrete patterns of expression associated with modeled complex disease states in animals (Tang et al, 2001). In addition, patterns of gene expression have been identified from blood samples obtained from a large number of healthy individuals, revealing surprising consistency in expression of genes associated with age, gender, and blood composition (Tang et al, 2001). Thus, it’s feasible that nucleated blood cells of alcohol-dependent individuals could show changes in gene expression that will provide a ‘signature’ of the disease. Discovery of reliable blood-based molecular markers of alcohol dependence and use would mark a milestone for addiction research and offer a great benefit for predicting the disease even without knowing the role of the markers in the disease process. Once biomarkers are discovered, the opportunity for early detection and intervention as well as personalized therapeutics should lead to new treatments for the disease.

Silent Heart Disease in Patients With Sleep Apnea-Hypopnea Syndrome: Usefulness of the Myocardial Performance Index

Sleep apnea-hypopnea syndrome (SAHS) is an emerging disease with considerable cardiovascular impact. The myocardial performance index (MPI) is an echocardiographic parameter that is useful in the assessment of global myocardial function. The purpose of this study was to identify any differences in the MPI between patients with and without SAHS. We studied 120 consecutive patients referred to our department for suspected SAHS. Following the overnight sleep study and after excluding all patients with hypertension, heart disease, or invalid recordings, 54 patients with SAHS and 13 patients without the disease matched for age and body mass were analyzed. A blinded cardiologist performed Doppler echocardiography, measuring parameters related to ventricular hypertrophy, systolic function, diastolic function, and the MPI. The data were compared by chi(2) and analysis of variance. Mean (SD) ventricular mass was greater in patients with SAHS (183.17 [40.5] g) than in those without that diagnosis (149 [26] g) (P=.005). No differences were observed in systolic function (78.5% [8.95%] vs 81.6% [7%]) (P=.2), although a higher percentage of patients with SAHS had abnormal diastolic function (71.2% vs 38.5%) (P=.049). The MPI was significantly higher in SAHS patients (0.54 [0.12] vs 0.46 [0.07]) (P=.028). On its own, SAHS leads to left ventricular hypertrophy. Diastolic involvement is common in these patients, although a large number of healthy individuals who are obese also present it. The MPI is higher in SAHS and could be a useful parameter to identify patients with silent heart disease before it progresses.

The Cutter Incident: How America’s First Polio Vaccine Led to the Growing Vaccine Crisis

By Paul A. Offit New Haven:Yale University Press, 2005. 238 pp. ISBN: 0-300-10864-8, $27.50 This entertaining, well-written book provides valuable insights into three interrelated areas, all built around the story of the Cutter incident, a landmark case that in some ways continues to have implications for product liability and the health of the vaccine industry today. The author, Paul Offit, has an admirable ability to present complicated issues in a way that is easy to understand for both technical and nontechnical audiences, and the book should (and does) have wide appeal. The first part of the story deals with the actual incident, which involved the failure to completely inactivate the very first lots of inactivated poliovaccine licensed for use in the United States, and the resulting epidemic of iatrogenic paralytic polio. This incident holds many lessons for us today. Offit shows how the ultimate outbreak was really the consequence of multiple factors: an inactivation procedure that was not completely understood by the manufacturers, testing algorhythms that were relatively insensitive for detection of remaining live virus in the final preparations, the use of an extremely virulent virus as the starting material for one of the three strains, and, most unpredictable of all, the enormous consequences of a seemingly trivial process change—the substitution of glass filters in a critical step in the processing of the culture lysates. Most disasters are the result of multiple synergistic failures, not all of which are predictable, and the Cutter incident is a good illustration of this. The second part of the story describes the resulting product liability trial, in which the manufacturer of the vaccine, Cutter Laboratories, was found to be liable even though it was not negligent. Cutter followed all available guidelines in production of the vaccine and only released lots that had passed recommended safety tests. However, the vaccine, rather than preventing polio as it was supposed to do, actually caused polio instead. In the trial, the jury did not find Cutter to have been negligent in the manufacture of the vaccine. However, Cutter was found to have violated the implied warranty that its product, when used as directed, would be safe and effective for its intended purpose. The author makes a convincing argument that this case set a precedent for liability without negligence that ultimately almost destroyed the vaccine industry in the United States. Only the Vaccine Injury Compensation Program, in which claims against manufacturers are first arbitrated by a panel of experts, has kept manufacturers in the game. The third part of the story is a more speculative discussion of the role product liability has played in the currently tenuous situation facing our supply of critical vaccines in the United States. This complex situation involves not only product liability but the economics of the marketplace, the role of government funding for vaccines, and probably other issues as well. However, product liability clearly also plays a role, and continues to have an impact today. For example, legislation protecting manufacturers of potential pandemic vaccines against product liability claims has emerged as a critical issue, which will be required for adequate control of the current avian influenza threat, much as it was in 1976. Thimerosal, which has now been convincingly demonstrated to have no association with neurodevelopmental disorders, has in the meantime continued to be a source of liability claims and state legislation. Vaccines have had a profound influence on human health and have been responsible for the complete elimination of smallpox, the elimination of measles and polio transmission in the Western Hemisphere, and many other benefits. However, to be effective, vaccines must be administered to very large numbers of healthy individuals. For this reason, vaccine safety always has been, and will remain, a preeminent concern among those involved in controlling human disease. This book should be of value to anyone who must deal with issues related to exposure of large populations to interventions.

Basement membrane protein and matrix metalloproteinase deregulation in engineered human oral mucosa following infection with Candida albicans

A variety of morphological changes in the basement membrane (BM) are known to occur in inflammatory diseases. Modifications of the BM can be associated with significant changes in protein content. Candida albicans (C. albicans) is normally a commensal organism and is a member of the natural flora of a large number of healthy individuals. However, under certain conditions, C. albicans can invade host tissues, causing inflammation and tissue damage. The aim of this study was to investigate the effect of C. albicans on the expression and production of structural (laminin-5 and type IV collagen) and inflammatory [matrix metalloproteinases (MMPs) and their inhibitors] proteins by human oral epithelial cells. Using engineered normal human oral mucosa infected with 10(5) C. albicans/cm2 for different periods of time, we were able to demonstrate that this yeast promotes significant laminin-5 and type IV collagen gene activation and protein secretion. These effects were accompanied by MMP-2 and MMP-9 gene activation. Interestingly, only the levels of active MMP-9 rose. The increase in MMP levels was paralleled by a decrease in the secretion of type 2 matrix metalloproteinase tissue inhibitors (TIMP-2). Our results demonstrated that C. albicans has a significant effect on tissue structure through BM protein and MMP modulation. This might help C. albicans overcome the mechanical and biological defenses of the tissue and allow it to disseminate, causing severe infections. If C. albicans uses MMPs (mainly MMP-9) to disseminate, inhibition of this protease could be of interest in treating a variety of inflammatory disorders, including oral candidiasis.

Anorectal functional testing: review of collective experience.

Anorectal manometry includes a number of specific tests that are helpful in the diagnostic assessment of patients with fecal incontinence and constipation; their purpose is to delineate the pathophysiological mechanism for these symptoms. Some of these tests may also provide helpful information in the assessment of patients with rectal pain or diarrhea, but their sensitivity and specificity are less well established for these symptoms. Tests for which there is consensus regarding their clinical utility include 1) resting anal canal pressure, 2) anal canal squeeze pressure (peak pressure and duration), 3) the rectoanal inhibitory reflex elicited by balloon distension of the rectum, 4) anal canal pressure in response to a cough, 5) anal canal pressure in response to defecatory maneuvers, 6) simulated defecation by means of balloon or radiopaque contrast, 7) compliance of the rectum in response to balloon distension, and 8) sensory thresholds in response to balloon distension. Anal endosonography and pelvic floor electromyography from intra-anal plate electrodes are nonmanometric tests that are also specifically useful in the evaluation of constipation and fecal incontinence. The clinical utility of all anorectal manometric tests is limited by the relative absence of 1) standardization of test protocols and 2) normative data from a large number of healthy individuals. The interpretation of these diagnostic tests is also complicated by the fact that patients are able to compensate for deficits in specific physiological mechanisms maintaining continence and defecation by utilizing other biological and behavioral mechanisms.

The evolution, evaluation and interpretation of antiphospholipid antibody assays

aPA have been observed in a variety of clinical settings, many of which are associated with thrombotic events in the venous, arterial or placental circulation. Although many assays have evolved to detect aPA the most sensitive ones are those that use the following: 1) bovine serum as a blocking and/or diluting supplement, 2) multiple phospholipid antigens (CL, PS and PE), and 3) conjugates to detect several antibody isotypes (IgG, IgA and IgM). The reported variation in aPA detection is significant; therefore, it is important to test a large number of healthy individuals with the aPA ELISA to determine which patient ELISA values are above normal compared to the local population. Inasmuch as individual assays vary this will ensure that an elevated aPA value in one lab is comparable to an elevated aPA value in another laboratory. As laboratories continue to standardize individual assays both internally and externally, concurrence among laboratories should increase.

Dermographism: A review

Urticaria is one of the more common skin conditions seen by physicians. Physical agents are an important cause of urticaria, with pressure or shearing forces being the most common. Dermographism is due to a combination of pressure and shearing forces and is present in a large number of healthy individuals. The purpose of this article is to provide a review of dermographism and its clinical variants.

Funktionsdiagnostik des gesunden und kranken Herzens, Beziehungen zwischen Herzgrösse und Leistung

Physical training improves the performance of the heart. Recent studies of Sjostrand and other Swedish physiologists have shown that training increases the stroke volume and the volume of the heart. This implies that a small but healthy heart functions inefficiently, and that a certain amount of cardiac dilatation and hypertrophy, induced by training, may be beneficial. Reindell and his colleagues from Heidelberg conclude that cardiac performance during strenuous exercise is a function of the heart volume. Therefore, they have correlated the heart volume with the blood pressure, heart rate, electrocardiogram, ventilation, and oxygen uptake per beat during exercise in a large number of healthy individuals and in cardiac patients. The monograph contains a large number of tables and graphs with the detailed results of these correlations in men and women of various ages. The authors estimate the heart volume at rest from the supine, anteroposterior, and lateral x-ray films of