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PubMed2006

Molecular diagnostics: a historical perspective.

The rapid growth in molecular diagnostic testing, which has averaged between 10% and 20% per year for the past 5 years, is largely attributable to both breakthroughs in our basic understanding (i.e., the Human Genome Project) and in applied technology. In the past decade, molecular applications have moved from labor-intensive and manual to rapid and automated due to improvements in sample extraction, target amplification, and sensitive and specific detection schema. This review describes some of the more significant technological milestones of the past 10 years and, when tied to basic and applied research, how these have led to important clinical applications. The next decade promises even more exciting technologies and applications for the field of molecular laboratory medicine.

Clinical Laboratory Techniques↗
PubMed2005

Decreasing age at prostate cancer diagnosis over successive generations in prostate cancer families.

BACKGROUND: The decline in age at prostate cancer diagnosis over the past decade is partially attributable to prostate specific antigen (PSA) screening. We examined age at diagnosis over successive generations within prostate cancer families. METHODS: Families with at least two affected men were selected from the University of Michigan Prostate Cancer Genetics Project. The 1,345 individuals from 489 families were grouped into three generations. RESULTS: Risk of prostate cancer diagnosis at a given age was estimated to increase 1.31 (95% CI: 1.13-1.51) times from one generation to the next. Among men diagnosed prior to the PSA era, inferences were similar (hazard ratio = 1.28, 95% CI: 0.97-1.68). No maternal versus paternal disease transmission effect was observed. CONCLUSIONS: Age at prostate cancer diagnosis was observed to decrease over successive generations in families from an ongoing familial prostate cancer study. This finding, if confirmed, may have important implications for familial prostate cancer risk assessment.

Age Distribution↗
PubMed1997

Sensitization during visual habituation sequences: procedural effects and individual differences.

Although individual differences in visual habituation have long been interpreted in terms of processes derived from comparator theory, research over the last decade has suggested that arousal or arousability as manifest in sensitization may contribute to infants' attentional profiles, and thus, to individual differences in those profiles. We explored this possibility by habituating 4-month-old infants to 4 x 4, 10 x 10, or 20 x 20 checkerboards in a fixed-trial paradigm. The first specific aim was to examine the attentional characteristics of infants with habituation patterns showing sensitization versus those that did not. The second specific aim was to determine whether patterns of attention suggestive of sensitization effects reported in past research might be attributable to the use of illuminated interstimulus intervals (ISIs). Trends were observed for sensitization to occur more frequently with more complex than with less complex checkerboards. Infants who showed looking patterns characteristic of sensitization looked longer and did not habituate as readily as infants who did not show sensitization. Finally, different ISIs did not engender different levels of sensitization, but dark ISIs significantly increased infants' looking times to stimuli during trials.

Arousal↗
PubMed1987

Prevalence of leptospirosis in man. Pilot survey.

A survey on the prevalence of leptospirosis was performed on the population living in an area of central Italy. The size of the sample was calculated in order to provide significant results in the case of a prevalence of infection in not less than 1% of the population. Results demonstrated an unexpectedly wide circulation of leptospirosis in the surveyed area, showing a prevalence rate of infection of 11.34% for people living in rural areas and 3.08% for people living in the main town. The highest prevalence of infection (17.44%) was found in people between 30 and 44 years of age, living in rural areas. Such a wide circulation of undiagnosed past leptospiral infections was attributed both to the prevalence of mild clinical cases of leptospirosis in humans and the lack of microbiological tests performed to differentiate current leptospirosis from other infectious illnesses. An unexpected persistence in sera of co-agglutinins towards non-pathogenic serovars of L. biflexa was also noticed in healthy people. Criteria were established for the extension of the survey on the prevalence of leptospirosis to cover larger areas by limiting sampling to the more exposed age groups and to areas representative of a larger land belt.

Adolescent↗
PubMed2005

The impact of laparoscopy on bariatric surgery.

The rising popularity of bariatric surgery over the past several years is attributable in part to the development of laparoscopic bariatric surgery. Morbidly obese patients have associated comorbid conditions that may predispose them to postoperative morbidity. The laparoscopic approach to bariatric surgery offers a minimally invasive option that reduces the physiologic stress and provides clinical benefits, as compared with the open approach. This review summarizes the impact of laparoscopic surgery on bariatric surgery, the various risk factors that could potentially predispose morbidly obese patients to postoperative morbidity, the fundamental differences between laparoscopic and open bariatric surgery, and the physiology of reduced tissue injury associated with laparoscopic bariatric surgery.

Bariatric Surgery↗
PubMed1991

Longitudinal Gompertzian analysis of primary malignant brain tumor mortality in the U.S., 1962-1987: rising mortality in the elderly is the natural consequence of competitive deterministic dynamics.

Age-adjusted mortality rates for primary malignant brain tumors (PMBT) in the United States from 1962 to 1987 were subjected to longitudinal Gompertzian analysis. Age-adjusted PMBT mortality rate distributions between age 25 and 65 years were determined by a variable environmental factor and a common intersect point. The environmental factor declined (improved) 1.58-fold for men and 2.34-fold for women in 1987 as compared to 1962. The age at the common intersect point was 68.4 years for men and 64.1 years for women. Between 1962 and 1987, non-age-standardized annual crude PMBT mortality rates increased 14.5% for men and 37.8% for women. However, PMBT mortality rates at age 77.5 years rose 259% for men and 409% for women between 1962 and 1987. Longitudinal Gompertzian analysis of PMBT mortality data suggests that rapidly rising PMBT mortality rates in the elderly are the natural consequence of competitive deterministic mortality dynamics and should not be attributed to environmental factors, past or present, that are directly contributing to PMBT mortality. Furthermore, longitudinal Gompertzian analysis demonstrates that PMBT mortality should not be studied in isolation, but rather should be examined in relation to other causes of death. When viewed from this perspective, the basis for the dramatic rise in PMBT mortality in the elderly becomes quite evident.

Adult↗
PubMed1990

Terminal notching of the QRS complex in V1 and V2 in seborrheic patients.

Widening of the QRS complex by terminal notching in leads V1 and V2 was observed in 6 seborrheic patients with adequate personal hygiene. This anomaly disappeared when the presternal skin was degreased thoroughly with cationic detergent before placing the conductive paste and electrodes. We attribute these electrocardiographic alterations to variations in the apocrine secretions in the presternal region, which modified the resistance of the skin to electrical potentials.

Acne Vulgaris↗
PubMed1991

Epidemiology of vaginitis.

Vaginitis is one of the most common problems in clinical medicine, and it is the reason cited most often for visits to obstetricians and gynecologists. This article reviews the epidemiology in the United States and Scandinavia for the three major causes of vaginitis: candidiasis, trichomoniasis, and bacterial vaginosis. The incidence of candidiasis has increased dramatically during the past decade, with an increase in the percentage of non-albicans Candida strains. However, in Scandinavia the incidence of candidiasis has been relatively stable, between 10% and 30%, during the past 5 years. The incidence of Trichomonas has decreased dramatically in both the United States and Scandinavia during the past 15 years, partly attributable to the advent of metronidazole. In the United States bacterial vaginosis continues to be the leading variety of vaginal infection, affecting a broader spectrum of women than gonorrhea. The prevalence of bacterial vaginosis in Scandinavia is about 30%, and this percentage increases with age according to studies of patients at sexually transmitted disease clinics.

Adolescent↗
PubMed1999

Women's satisfaction with birth control: a population survey of physical and psychological effects of oral contraceptives, intrauterine devices, condoms, natural family planning, and sterilization among 1466 women.

User satisfaction and the physical and psychological effects of five commonly used contraceptive methods were investigated in a population survey among 1466 West German women. The focus was on effects attributed by current and past users to these methods, rather than objectively assessed effects, to shed further light on personal experiences that are highly relevant to the user but often remain unknown to prescribers and unreported in the medical literature. Within the overall sample, 1303 women were surveyed concerning their current or past use of oral contraceptives (OC), 996 regarding condoms, 342 with respect to intrauterine devices (IUD), 428 in regard to natural family planning (NFP), and 139 in relation to sterilization (respondents completed questions about each method used). It emerged that satisfaction was greatest with sterilization (92% of users), followed by OC (68% of ever users), IUD (59%), NFP (43%), and condoms (30%). Almost one in three NFP users had experienced an unwanted pregnancy during use of this method, as compared with one in 20 OC and condom users. The majority of users reported no mood changes during use of the methods studied. The percentages reporting negative mood changes (various items were scored) were up to 16% among OC users, 23% among condom users, and 30% among NFP users. The latter observations suggested that subjective side effects of a contraceptive agent on mood generally reflected, at least in part, the user's sense of confidence in the method concerned (notably, with regard to efficacy and safety). Oral contraceptives, IUD, and sterilization had a broadly positive impact on sex life, whereas that of condoms was often negative. Whereas OC users often reported less heavy and painful menstruation (in up to 56% of cases), IUD were associated with heavier, prolonged, and more painful menstruation (in up to 65% of cases), as also was sterilization, although to a lesser extent (in up to 32% of cases). Overall, the study findings indicated that OC and sterilization had less negative impact on physical and psychological functioning than the other methods studied, in contrast to what the general public often believes.

Adult↗
PubMed2001

Health and productivity: a role for occupational health professionals.

The impressive economic gains achieved by many nations within the past decade have been attributed primarily to improvements in productivity from technological changes. The resultant low unemployment levels, however, emphasize the importance of human capital in the success of any enterprise. Concurrently, some economists have proposed an alternative economic view regarding the relationship between health and income, postulating that improvements in the health of the nation's population have a substantial effect on its economic viability. Such a view directly pertains to occupational health professionals, who are often charged with promoting the health of the worker. Although studies relating the beneficial impact of occupational health on productivity and human performance are limited, some efforts have shown impressive effects, as measured primarily by reduced absenteeism. The prompt, assertive management of occupational injuries and illnesses and their treatment have been well documented. Illnesses not considered traditional occupational ailments, such as migraine headaches, allergic disorders, infectious diseases, and depression, offer opportunities for occupational health professionals to ensure an accurate diagnosis and proper treatment for minimizing the impact on work performance. Considerable opportunities exist for occupational health professionals to demonstrate the importance of certain services to productivity.

Absenteeism↗
PubMedDate not supplied

Creating the Management Academy for Public Health: relationships are primary.

True collaboration among large federal agencies is rare, as is that among large and influential national foundations. The collaboration between two major government health agencies (The Centers for Disease Control and Prevention and the Health Resources and Services Administration) and three major health foundations (the W.K. Kellogg Foundation, the Robert Wood Johnson Foundation, and the CDC Foundation) to create the Management Academy for Public Health is unprecedented in public health over the past quarter century. We attribute this success to the unique combination of a strong foundation of relationships between the partners and a commitment to generative dialogue throughout the design and implementation of the program. The success and sustainability of the Academy derive directly from these critical success factors, serving as an exemplary model for future collaborative endeavors.

Centers for Disease Control and Prevention, U.S.↗
PubMed2003

Self-organizing neural systems based on predictive learning.

The ability to predict future events based on the past is an important attribute of organisms that engage in adaptive behaviour. One prominent computational method for learning to predict is called temporal-difference (TD) learning. It is so named because it uses the difference between successive predictions to learn to predict correctly. TD learning is well suited to modelling the biological phenomenon of conditioning, wherein an organism learns to predict a reward even though the reward may occur later in time. We review a model for conditioning in bees based on TD learning. The model illustrates how the TD-learning algorithm allows an organism to learn an appropriate sequence of actions leading up to a reward, based solely on reinforcement signals. The second part of the paper describes how TD learning can be used at the cellular level to model the recently discovered phenomenon of spike-timing-dependent plasticity. Using a biophysical model of a neocortical neuron, we demonstrate that the shape of the spike-timing-dependent learning windows found in biology can be interpreted as a form of TD learning occurring at the cellular level. We conclude by showing that such spike-based TD-learning mechanisms can produce direction selectivity in visual-motion-sensitive cells and can endow recurrent neocortical circuits with the powerful ability to predict their inputs at the millisecond time-scale.

Action Potentials↗
PubMed2004

The increased prevalence of allergy and the hygiene hypothesis: missing immune deviation, reduced immune suppression, or both?

Allergic atopic disorders, such as rhinitis, asthma, and atopic dermatitis, are the result of a systemic inflammatory reaction triggered by type 2 T helper (Th2) cell-mediated immune responses against 'innocuous' antigens (allergens) of complex genetic and environmental origin. A number of epidemiological studies have suggested that the increase in the prevalence of allergic disorders that has occurred over the past few decades is attributable to a reduced microbial burden during childhood, as a consequence of Westernized lifestyle (the 'hygiene hypothesis'). However, the mechanisms by which the reduced exposure of children to pathogenic and nonpathogenic microbes results in enhanced responses of Th2 cells are still controversial. The initial interpretation proposed a missing immune deviation of allergen-specific responses from a Th2 to a type 1 Th (Th1) profile, as a result of the reduced production of interleukin-12 and interferons by natural immunity cells which are stimulated by bacterial products via their Toll-like receptors. More recently, the role of reduced activity of T regulatory cells has been emphasized. The epidemiological findings and the experimental evidence available so far suggest that both mechanisms may be involved. A better understanding of this question is important not only from a theoretical point of view, but also because of its therapeutic implications.

Animals↗
PubMed2003

Interstitial cells: involvement in rhythmicity and neural control of gut smooth muscle.

Many smooth muscles display spontaneous electrical and mechanical activity, which persists in the absence of any stimulation. In the past this has been attributed largely to the properties of the smooth muscle cells. Now it appears that in several organs, particularly in the gastrointestinal tract, activity in smooth muscles arises from a separate group of cells, known as interstitial cells of Cajal (ICC), which are distributed amongst the smooth muscle cells. Thus in the gastrointestinal tract, a network of interstitial cells, usually located near the myenteric plexus, generates pacemaker potentials that are conducted passively into the adjacent muscle layers where they produce rhythmical membrane potential changes. The mechanical activity of most smooth muscle cells, can be altered by autonomic, or enteric, nerves innervating them. Previously it was thought that neuroeffector transmission occurred simply because neurally released transmitters acted on smooth muscle cells. However, in several, but not all, regions of the gastrointestinal tract, it appears that nerve terminals, rather than communicating directly with smooth muscle cells, preferentially form synapses with ICC and these relay information to neighbouring smooth muscle cells. Thus a set of ICC, which are distributed amongst the smooth muscle cells of the gut, are the targets of transmitters released by intrinsic enteric excitatory and inhibitory nerve terminals: in some regions of the gastrointestinal tract, the same set of ICC also augment the waves of depolarisation generated by pacemaker ICC. Similarly in the urethra, ICC, distributed amongst the smooth muscle cells, generate rhythmic activity and also appear to be the targets of autonomic nerve terminals.

Animals↗
PubMed1992

Tuberous sclerosis presenting as a suspicious sudden death--a case report and review of sudden deaths in epilepsy.

A case of a suspicious sudden death in a 19-year-old Caucasian female epileptic is presented. The brain showed characteristic lesions of tuberous sclerosis. In most sudden deaths in idiopathic epilepsy no causative lesion is found in the brain. A review of the past five years' cases attributed to sudden deaths in epilepsy from our department is presented, with particular reference to findings which might be construed as suspicious, e.g., signs of asphyxia and bruising in neck muscles, and to findings which support the diagnosis, e.g. biting of the tongue, voiding of urine, low levels of medication.

Adolescent↗
PubMed2005

Evaluation of the toll-like receptor 6 Ser249Pro polymorphism in patients with asthma, atopic dermatitis and chronic obstructive pulmonary disease.

BACKGROUND: For allergic disorders, the increasing prevalence over the past decade has been attributed in part to the lack of microbial burden in developed countries ('hygiene hypothesis'). Variation in genes encoding toll-like receptors (TLRs) as the receptor system for the first innate immune response to microbial stimuli has been implicated in various inflammatory diseases. We evaluated here the role of a coding variation, Ser249Pro, in the TLR6 gene in the pathogenesis of asthma, atopic dermatitis (AD) and chronic obstructive pulmonary disease (COPD). METHODS: Genotyping of the Ser249Pro polymorphism in 68 unrelated adult patients and 132 unrelated children with asthma, 185 unrelated patients with COPD, 295 unrelated individuals with AD and 212 healthy control subjects was performed by restriction enzyme digestion. RESULTS: We found a weak association of the 249Ser allele with childhood asthma (p = 0.03). Yet, significance was lost after Bonferroni correction. No association was evident for AD or COPD. CONCLUSION: Variation in TLR6 might play a role in the pathogenesis of childhood asthma.

Adolescent↗
PubMed1980

A comparison of scoring systems and level of scorer experience on the Bender-Gestalt Test.

Compared the usefulness of four scoring approaches to the Bender-Gestalt Test (Hain, Hutt-Briskin, Pauker, and number of rotations) on the same sample of 50 mixed, psychiatric inpatients. Also, the accuracy of scorers of varying levels of experience was compared. Twelve different scorers were used representing three levels of expertise: "expert," "typical," and "novice." For a measure of reliability and two measures of diagnostic discrimination the Hutt-Briskin and Pauker systems were more successful than the Hain system or number of rotations. For each scoring system there were no differences in diagnostic accuracy attributable to level of past experience. It was recommended that the findings on the Pauker system be cross-validated before being used in clinical settings.

Adolescent↗