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PubMed2002

Study design for concurrent development, assessment, and implementation of new diagnostic imaging technology.

With current constraints on health care resources and emphasis on value for money, new diagnostic imaging technologies must be assessed and their value demonstrated. The state of the art in the field of diagnostic imaging technology assessment advocates a hierarchical step-by-step approach. Although rigorous, such a hierarchical assessment is time-consuming, and, given the current rapid advances in technology, results are often too late to influence management and policy decisions. The purpose of this article is to discuss a study design in which development, assessment, and implementation of new diagnostic imaging technology take place concurrently in one integrated process. An empirically based pragmatic study design is proposed for imaging technology assessment. To minimize bias and enable comparison with current technology, a randomized controlled design is used whenever feasible and ethical. Outcome measures should reflect the clinical decision-making process based on imaging information and acceptance of the new test. Outcome measures can include additional imaging studies requested, costs of diagnostic work-up and treatment, physicians' confidence in therapeutic decision making, recruitment rate, and patient outcome measures related to the clinical problem. The key feature of the proposed study design is analysis of trends in outcome measures over time.

Decision Making↗
PubMed2006

Proteomics and genomics of microgravity.

Many serious adverse physiological changes occur during spaceflight. In the search for underlying mechanisms and possible new countermeasures, many experimental tools and methods have been developed to study microgravity caused physiological changes, ranging from in vitro bioreactor studies to spaceflight investigations. Recently, genomic and proteomic approaches have gained a lot of attention; after major scientific breakthroughs in the fields of genomics and proteomics, they are now widely accepted and used to understand biological processes. Understanding gene and/or protein expression is the key to unfolding the mechanisms behind microgravity-induced problems and, ultimately, finding effective countermeasures to spaceflight-induced alterations. Significant progress has been made in identifying the genes/proteins responsible for these changes. Although many of these genes and/or proteins were observed to be either upregulated or downregulated, however, no large-scale genomics and proteomics studies have been published so far. This review aims at summarizing the current status of microgravity-related genomics and proteomics studies and stimulating large-scale proteomics and genomics research activities.

Animals↗
PubMed1996

Safety aspects of local endobronchial allergen challenge in asthmatic patients.

Local endobronchial allergen challenge is being increasingly used to investigate the role of allergic inflammation in asthma. However, little information is available about the safety of this procedure and the changes induced in airway physiology. BAL and biopsy were performed at 10 min and at 4 to 6 h, or 24 h after segmental allergen challenge in 49 patients with atopic asthma. Two hours after challenge, FEV1 was reduced from 97.6 +/- 13.9 (mean +/- SD) to 83.4 +/- 21.7% predicted. FEV1 remained reduced at 4 to 6 h (87.7 +/- 20.4%), but it had nearly returned to baseline by 24 h (93.2 +/- 14.0%). When endobronchial challenge was combined with BAL and biopsy, the initial fall in FEV1 was slightly greater (from 101.8 +/- 14.2 to 78.5 +/- 13.6%). Bronchial responsiveness to methacholine was measured in 10 subjects, and it showed a twofold increase 24 h after local challenge and lavage. Significant changes in FEV1 and methacholine PC20 were still detectable 72 h after challenge. Widespread wheezing occurred in 29% of the subjects, but none of the them had to be admitted to hospital. We conclude that local endobronchial allergen challenge, although producing measurable changes in airway physiology, is in general well tolerated and is an acceptable method to investigate airway pathophysiologic processes in patients with mild to moderate asthma.

Adult↗
PubMed1995

Fluid absorption in isolated perfused colonic crypts.

A spatial segregation of ion transport processes between crypt and surface epithelial cells is well-accepted and integrated into physiological and pathophysiological paradigms of small and large intestinal function: Absorptive processes are believed to be located in surface (and villous) cells, whereas secretory processes are believed to be present in crypt cells. Validation of this model requires direct determination of fluid movement in intestinal crypts. This study describes the adaptation of techniques from renal tubule microperfusion to hand-dissect and perfuse single, isolated crypts from rat distal colon to measure directly fluid movement. Morphologic analyses of the isolated crypt preparation revealed no extraepithelial cellular elements derived from the lamina propria, including myofibroblasts. In the basal state, crypts exhibited net fluid absorption (mean net fluid movement = 0.34 +/- 0.01 nl.mm-1.min-1), which was Na+ and partially HCO3- dependent. Addition of 1 mM dibutyryl-cyclic AMP, 60 nM vasoactive intestinal peptide, or 0.1 mM acetylcholine to the bath (serosal) solution reversibly induced net fluid secretion (net fluid movement approximately -0.35 +/- 0.01 nl.mm-1.min-1). These observations permit speculation that absorption is a constitutive transport function in crypt cells and that secretion by crypt cells is regulated by one or more neurohumoral agonists that are released in situ from lamina propria cells. The functional, intact polarized crypt described here that both absorbs and secretes will permit future studies that dissect the mechanisms that govern fluid and electrolyte movement in the colonic crypt.

Animals↗
PubMed2006

Starting point to molecular design: efficient automated 3D model builder Key3D.

Obtaining three-dimensional (3D) structures from structural formulae is a crucial process in molecular design. We have developed a new 3D model builder, Key3D, in which the simplified distance geometry technique and structure optimization based on the MMFF force field are combined. In an evaluation study using 598 crystal structures, the high performance and accuracy of Key3D were demonstrated. In the "flexible-fitting" test, which is focused on practical usefulness in the molecular design process, 88% of the Key3D structures acceptably reproduced the reference crystal structures (root-mean-square deviation <0.6 A) upon rotation of acyclic bonds. These results indicate that Key3D will be very effective in providing starting points for practical molecular design.

Algorithms↗
PubMed2002

Living with vitiligo: dealing with difference.

OBJECTIVES: Individuals with a disfigurement are at risk of experiencing psychological distress, but the level of this distress is only marginally associated with clinical severity. This study examines the experience of living with the skin condition vitiligo with a view towards understanding its impact and the ways in which participants deal with this chronic and disfiguring disease. DESIGN: The qualitative method Interpretative Phenomenological Analysis was used. METHODS: In a semi-structured interview, seven white female vitiligo sufferers were asked to describe their experiences from the time the vitiligo first became apparent to the time of the interview. They were encouraged to elaborate on their own reactions and how they dealt with the reactions of others. RESULTS: Initially, participants felt overwhelmed by their illness but over time they developed several strategies in order to 'contain' their difference in appearance within manageable limits. The behavioural strategies of avoidance and concealment had several disadvantages, whereas cognitive strategies were less problematic but difficult to sustain consistently. Social support served to facilitate the development of coping methods associated with acceptance of difference. However, maintaining this acceptance was a struggle and the process fragile. CONCLUSIONS: Living with vitiligo was a continuous struggle. The results are consistent with Leventhal's (1970) notion that coping is a problem-solving process and with Moos and Schaefer's (1984) contention that dealing with a chronic disease involves the development of a variety of strategies in order to regain equilibrium. Further research is needed to examine whether the experiences described here are common to other disfiguring conditions.

Journal Article↗
PubMed1997

Bisphosphonate effects and the bone remodeling transient.

Published randomized clinical trial data for alendronate, given at a dose of 10 mg/day, were fitted by a computer algorithm to the currently accepted model of the bone remodeling process. The purpose was to determine how much of the reported improvement in lumbar spine bone density could be attributed to the inevitable remodeling transient and how much might represent positive bone balance. Very good fits to the clinical data were easily obtained, indicating the general validity of current syntheses of bone remodeling biology. The best fit was provided by simulations produced by combinations of 36-38% suppression of remodeling activation and positive remodeling balance ranging from 1.1 to 1.4% per year. Whole body bone biomarker changes would have suggested both a slightly greater degree of suppression and a higher baseline level of remodeling than could be provided by any of the simulations if they were to fit the clinical data. Either regional skeletal heterogeneity or lack of a one-to-one quantitative relationship between remodeling changes and biomarker changes may explain the discrepancies between the two approaches.

Alendronate↗
PubMed2001

Psychoanalysis and cognitive behaviour therapy--rival paradigms or common ground?

The author suggests that contemporary enthusiasm for cognitive-behavioural therapy reflects our longing for swift, rational help for psychological suffering. Competition for funding threatens the psychoanalytic presence in the public sector. The psychoanalytic and cognitive-behavioural models are contrasted, and the relative richness of the psychoanalytic paradigm outlined. The author suggests that a cognitive model is commonsensical, but less complex, with less potential explanatory and therapeutic power. She discusses how the analytic stance is always under pressure to 'collapse' into simpler modes, one of which resembles a cognitive one. This also occurs inevitably, she argues, when attempts are made to 'integrate' the two models. Cognitive and 'integrated' treatments nevertheless have the advantage that they are less intrusive and hence more acceptable to some patients. Selected empirical process and outcome research on cognitive and psychoanalytic therapies is discussed. Brief psychotherapies of either variety have a similar, modestly good outcome, and there is some evidence that this may be based more on 'dynamic' than 'cognitive' elements of treatment. Formal outcome studies of more typical psychoanalytic psychotherapy and of psychoanalysis itself begin to suggest that these long and complex treatments are effective in the more comprehensive ways predicted by the model.

Cognitive Behavioral Therapy↗
PubMed2004

Direct discrimination between models of protein activation by single-molecule force measurements.

The limitations imposed on the analyses of complex chemical and biological systems by ensemble averaging can be overcome by single-molecule experiments. Here, we used a single-molecule technique to discriminate between two generally accepted mechanisms of a key biological process--the activation of proteins by molecular effectors. The two mechanisms, namely induced-fit and population-shift, are normally difficult to discriminate by ensemble approaches. As a model, we focused on the interaction between the nuclear transport effector, RanBP1, and two related complexes consisting of the nuclear import receptor, importin beta, and the GDP- or GppNHp-bound forms of the small GTPase, Ran. We found that recognition by the effector proceeds through either an induced-fit or a population-shift mechanism, depending on the substrate, and that the two mechanisms can be differentiated by the data.

Elasticity↗
PubMed1998

Non increased neuron-specific enolase concentration in cerebrospinal fluid during first febrile seizures and a year follow-up in pediatric patients.

Febrile seizures are the commonest acute neurological disorder of early childhood. Studies suggested that febrile seizures are previous acute events from a more serious neurological problem. Due to neuron-specific enolase is generally accepted as a marker for neuropathological processes in the brain, 16 pediatric patients were studied during their first seizures and a year after it. Neuron-specific enolase in cerebrospinal fluid and blood were analysed by an immune enzyme assay. Non pathological neuron-specific enolase values were obtained in both periods in the group of patients. There were no significative differences when paired series statistics test was performed with 95% of confidence. Neuron-specific enolase appears not to be a marker for febrile seizures because its concentration not be increased in cerebrospinal fluid in this group of patients.

Cerebrospinal Fluid↗
PubMed2001

[Simplifying the sampling method for evaluating the larval density of Aedes aegypti in São Paulo State, Brazil].

OBJECTIVE: To suggest changes in the sampling procedures for estimating the larval density of Aedes aegypti in the state of São Paulo, Brazil, by assessing the efficacy and level of complexity of the current procedures. METHODS: The "Superintendência de Controle de Endemias do Estado de São Paulo" - SUCEN's (Superintendence for Endemic Control of the State of São Paulo) sampling procedures for estimating the density of Aedes aegypti larvae was assessed. The Breteau index with one-stage cluster sampling was applied. An average of 35 blocks, 14 buildings per block, of a total of 510 buildings per sample, were assessed. One hundred and eleven samples were obtained in 6 municipalities of São José do Rio Preto. RESULTS: The Breteau index estimates higher than 3 had coefficients of variation smaller than 30% in 71% of the samples. The design effect was 1.19 and 1.79 for indexes lower and higher than 5, respectively. The estimates were obtained in less than 3 days, requiring a daily average of 5.5 men per sampling. CONCLUSION: This sampling design revealed to be a simplified one: fast, economic and easily managed. The operational easiness was due to the use of the one-stage cluster sampling, when there was not need to prepare lists of addresses and then sort and locate the buildings. Though the design effect shows a slight loss of the estimates' accuracy with the use of one-stage cluster sampling, this was proven to be under acceptable range. Simplifying changes in the process of determining the sample size and assessing sampling errors are proposed.

Aedes↗
PubMed1977

Peer sex education training and evaluation.

Human sexuality has been recognized as an important developmental, emotional, and medical concern on the college campus. The Peer Sex Education Program at the University of Massachusetts/Amherst has been developed as a model for the use of trained students in an educational, referral, and counseling role. This paper describes the program and outlines the methodology used in the documentation and evaluation of various program aspects. Aspects described include the program's rationale and background, the recruiting process, roles and responsibilities, training and supervision models, community development, and delivery of service. Categories of documentation and evaluation considered include effort, performance, adequacy of performance, efficiency, and process. These are related to consumer acceptance and satisfaction, outcome measures of knowledge, attitude, and behavior, effectiveness of referral and other functions, and effect of program on the peer educators' growth and development. The allocation of energy and resources between program development, service delivery and evaluation needs is highlighted.

Humans↗
PubMed2005

[Initial assessment and transportation of an injured child].

OBJECTIVES: Since trauma has a great impact on mortality and preventable morbidity among children and adolescents, in addition to its social consequences, the aim of this study is to evaluate peculiarities regarding prehospital, in-hospital, and interhospital assessment of injured pediatric patients. SOURCES OF DATA: The Cochrane database was searched for systematic reviews and controlled trials, the MEDLINE and LILACS databases were used for the last 5 years, and review of older reference sections in significant publications using trauma, pediatric trauma, primary survey, secondary survey, in-hospital assessment, prehospital and transportation as keywords. SUMMARY OF THE FINDINGS: There are different strategies that constitute the systematic assessment of the injured pediatric patient. Nevertheless, almost all strategies involve knowing the peculiarities about the pediatric population, with regard to age, to the growth and development process, and finally, to the minimally acceptable and available resources. CONCLUSIONS: The most important principle is to do no further harm. If the peculiarities about airway maintenance, ventilation, circulation with hemorrhage control, disability, exposure up to secondary survey and preparation of prehospital and interhospital transportation are properly taken care of, better results will certainly be obtained.

Adolescent↗
PubMed1992

Medicare admission criteria for diabetes mellitus in Florida.

Medicare criteria for admission of patients to hospitals are the responsibility of Peer Review Organizations in each state. In 1986, in Florida, an attempt was made to introduce stricter than previously accepted admission criteria for diabetes mellitus. The new criteria were found to be unacceptable to many physicians and potentially dangerous. This article describes how a group of endocrinologists and diabetologists were able to impact on the Florida Peer Review Organization and change the criteria to allow for more acceptable standards without jeopardizing the review process.

Blood Glucose↗
PubMed2026

Metabolic depot for nucleated erythrocyte degradation: molecular and structural elucidation of the teleost melanomacrophage center.

The function of melanomacrophage centers (MMCs) has long been controversial. While their foundational function is widely accepted as "metabolic dumps" for waste processing, a widely circulated hypothesis posits that they are primitive germinal centers (GCs) executing adaptive immunity. To elucidate this controversy, this study systematically evaluated the splenic MMCs in a higher teleost ( Micropterus salmoides) by combining transmission electron microscopy (TEM) and high-resolution spatial transcriptomics. Structurally, TEM revealed that the MMC comprises a core with characteristic sparse cellular density, filled with cellular debris and encapsulated by a fibrous layer. Molecularly, under physiological conditions, MMC regions exhibited low transcriptional activity. We did not detect clear enrichment of B cell and T cell lineage genes, and the key GC marker aicda was not observed. Conversely, its predominant molecular signature was characterized by macrophage-driven iron metabolism (e.g., ferritin) and erythrocyte degradation (e.g., hba1). Furthermore, the physicochemical properties of MMCs pigments (e.g., argyrophilia) suggest that traditional histological staining methods warrant cautious interpretation regarding potential non-specific signals. In conclusion, our findings characterize the MMC as a highly specialized metabolic processing and sequestration niche. This study provides new perspectives on the evolution of immune-metabolic homeostasis in poikilothermic vertebrates, advances comparative immunology, and offers a critical scientific reference for the accurate interpretation of MMCs as a biological indicator in pathology and ecotoxicology.

Animals↗
PubMed2003

Computer simulation of prostate cryoablation--fast and accurate approximation of the exact solution.

OBJECTIVE: Cryosurgery is a minimally invasive cancer treatment that uses liquid nitrogen or supercooled argon to freeze and destroy tumors. To achieve complete ablation of the prostate, we have developed a computer program that can determine treatment effects by calculating iceball formation. This is based on a three-dimensional (3D) model of the patient's prostate constructed from ultrasound images. The program predicts the best set of cryoablation parameters and cryoprobe spatial positions, then displays these parameters in graphical or numerical form. The objective of this work was to improve our prostate cryoablation modeling software by making its partial differential equation (PDE) solver more accurate and faster. MATERIALS AND METHODS: CryoSim, our software package, accepts a set of acquired and processed 3D ultrasound images of the prostate, then models heat diffusion using numerical approximations of the heat equation. RESULTS: We describe the latest version of the CryoSim software, which models cryoablation therapy. Solving the problems of low spatial resolution (now down to a fraction of a millimeter, as compared to 5 mm in the old version) and modeling cryosurgery in a short time (down to few minutes versus hours) provides a platform for proper planning of cryosurgery and a tool for the training of surgeons. CONCLUSION: Changes in the PDE solver algorithm produce more accurate results, leading to an improved visualization of the iceball, with a precision of a few mm and a significant decrease in computation time.

Algorithms↗
PubMed2002

Use of an advanced formulation of beta-tricalcium phosphate as a bone extender in interbody lumbar fusion.

Despite numerous advances in the development of bone graft substitutes over the past 20 years, iliac crest autograft remains the gold standard for lumbar spinal fusion. However, donor site morbidity associated with the harvesting of iliac crest autograft remains problematic. Acute and chronic pain, prolonged operative time, bleeding, infection, deformity, and nerve and vascular injury still produce significant postoperative morbidity, even in the presence of careful surgical technique. Although allograft circumvents donor site morbidity, the growing number of spinal fusions performed in the United States and worldwide is creating a shortage of cadaver bone acceptable for use. Additionally, the extensive processing and storage of allograft is expensive. Synthetic materials, such as beta-tricalcium phosphate (beta-TCP), have been developed as alternatives to both autograft and allograft. A novel formulation of ultraporous beta-TCP (Vitoss, Orthovita, Malvern, Pa) offers interconnected microporosity, providing it with good wicking and hydrophilic properties. These properties allow the migration of nutrients, growth factors, and osteogenic cells into the ultraporous beta-TCP scaffold, thereby promoting new bone growth and concurrent scaffold resorption. This study presents a retrospective review of 7 patients who underwent anterior (ALIF) or posterior (PLIF) interbody fusion at 12 levels with a 3- to 6-month follow-up. At the patients' last radiographic examination, all 12 levels were solidly fused with interbody grafting material consisting only of allograft plus a combination of ultraporous beta-TCP and venous blood as an extender. Additionally, all 7 patients had segmental pedicle-screw fixation.

Adult↗
PubMed1994

Reengineering and improving the information-intensive work of patient tracking for inpatients and outpatients.

This article describes a CQI-driven effort to reengineer the tracking procedures for both inpatients and outpatients, refined to the extent that they have been identified as "best practices." The goal was to shift the work paradigm from a departmental focus to one that accepts work as a network of processes, but also to prepare for the new era of the electronic medical record, moving computer record keeping far closer to the point of care, requiring more precise recording of patient location.

Admitting Department, Hospital↗