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PubMed2004

A vaccine against Asian schistosomiasis.

There is continued transmission of schistosomiasis japonica in China and Philippines despite highly effective control programs that focus on the application of the highly effective drug praziquantel (PZQ). The massive Three Gorges Dam across the Yangtze River in Southern China, soon to be completed, is expected to significantly increase schistosomiasis transmission and introduce the disease into areas currently unaffected. After long-term experience it is generally accepted that PZQ chemotherapy, although the cornerstone of current control programs, does have significant limitations. Furthermore, efficient drug delivery requires a substantial infrastructure to regularly cover all parts of an endemic area. Although there is not yet clear-cut evidence for the existence of PZQ-resistant schistosome strains, decreased susceptibility to the drug has been observed in several countries. As a result, a protective vaccine represents an essential component for the long-term control of schistosomiasis. This article briefly reviews aspects of anti-schistosome protective immunity that are important in the context of vaccine development. The current status in the development of vaccines against Schistosoma japonicum will then be discussed as will new approaches that may improve on the efficacy of available vaccines, and aid in the identification of new targets for immune attack. With new and extensive data becoming available from the S. japonicum genome project, the prospects for developing an effective vaccine are encouraging. The challenges that remain are many but it is crucial that the momentum towards developing effective anti-schistosome vaccines is maintained.

Animals↗
PubMed1984

Acrosome reaction of human sperm used for in vitro fertilization.

The acrosomal reaction of human spermatozoa was assessed, according to a triple-stain technique, at the end of a 17-hour capacitation period in the search for a predictive test of sperm efficiency in an in vitro fertilization program. A 400% increase in the acrosomal reaction rate of the living spermatozoa was observed (4.2% +/- 3.2% before incubation versus 16% +/- 11% after incubation). No correlation could be evidenced between the abilities for spermatozoa to react and to fertilize mature human oocytes in vitro, whatever the initial semen quality. The acrosome reaction rate was not enhanced by the presence of the cumulus oocyte complex, by the selection of motile spermatozoa, or by the increase in albumin concentration of the culture medium.

Acrosome↗
PubMedDate not supplied

Reducing the noneducational and nonclinical workload of the surgical resident; defining the role of the health technician.

PURPOSE: Recent controversy over excessive resident work hours has prompted surgical educators and program directors to search for more efficient methods to limit the nonclinical and noneducational workload of surgical residents. Health technicians were employed at a large Veteran's Administration Medical Center to allow residents more time for direct patient care in the clinics and wards and in educational activities. METHODS: In a two-week period, daily data cards were collected from each intern and health technician identifying total hours spent in work, operations, clinics, and conferences. Each intern recorded the number and type of tasks performed and those tasks assigned to the health technician. The number and type of task performed were tabulated and averaged for each health technician and physician. RESULTS: Each intern (n = 3) and health technician (n = 8) completed 100% of the required data forms. In a control survey, each intern worked a mean of 16.9 hours per weekday and 5.0 hours per weekend day. With the addition of the health technicians, interns worked 12.9 hours per weekday and 6.8 hours per weekend day (when the health technicians were not present). Following the addition of the health technicians, resident time in the operating room increased from 3.3 hours per week to 9.8 hours per week. Each health technician aided the intern by performing an average of 20.25 tasks per day. CONCLUSIONS: This study shows that health technicians can be effective in reducing the overall hours and workload of surgical residents and increasing time spent in the operating room. Consideration should be given to including the health technician as integral members of the health care team in the teaching hospital.

Allied Health Personnel↗
PubMed1999

Recent information about hip dysplasia.

Dogs suffering from HD have a genetic background, but the releasing factors are many. Two of the most important are overnutrition and overexercising, especially in the young puppy. Radiography can give an estimate of the degree of secondary OA, and by evaluating the laxity in the hip joints at an early age, it seems to be possible to predict the chances for later development of OA. The eradication program has to be instituted in such a way that only the best dogs are accepted into breeding programs. It seems to be more efficient to eradicate the genetic part of the etiology by creating a breeding index by means of evaluating the offspring of the male dogs.

Animals↗
PubMed2001

Data mining in the US Vaccine Adverse Event Reporting System (VAERS): early detection of intussusception and other events after rotavirus vaccination.

The Vaccine Adverse Event Reporting System (VAERS) is the US passive surveillance system monitoring vaccine safety. A major limitation of VAERS is the lack of denominator data (number of doses of administered vaccine), an element necessary for calculating reporting rates. Empirical Bayesian data mining, a data analysis method, utilizes the number of events reported for each vaccine and statistically screens the database for higher than expected vaccine-event combinations signaling a potential vaccine-associated event. This is the first study of data mining in VAERS designed to test the utility of this method to detect retrospectively a known side effect of vaccination-intussusception following rotavirus (RV) vaccine. From October 1998 to December 1999, 112 cases of intussusception were reported. The data mining method was able to detect a signal for RV-intussusception in February 1999 when only four cases were reported. These results demonstrate the utility of data mining to detect significant vaccine-associated events at early date. Data mining appears to be an efficient and effective computer-based program that may enhance early detection of adverse events in passive surveillance systems.

Adverse Drug Reaction Reporting Systems↗
PubMed2003

Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data.

Quantification of mRNAs using real-time polymerase chain reaction (PCR) by monitoring the product formation with the fluorescent dye SYBR Green I is being extensively used in neurosciences, developmental biology, and medical diagnostics. Most PCR data analysis procedures assume that the PCR efficiency for the amplicon of interest is constant or even, in the case of the comparative C(t) method, equal to 2. The latter method already leads to a 4-fold error when the PCR efficiencies vary over just a 0.04 range. PCR efficiencies of amplicons are usually calculated from standard curves based on either known RNA inputs or on dilution series of a reference cDNA sample. In this paper we show that the first approach can lead to PCR efficiencies that vary over a 0.2 range, whereas the second approach may be off by 0.26. Therefore, we propose linear regression on the Log(fluorescence) per cycle number data as an assumption-free method to calculate starting concentrations of mRNAs and PCR efficiencies for each sample. A computer program to perform this calculation is available on request (e-mail: bioinfo@amc.uva.nl; subject: LinRegPCR).

Benzothiazoles↗
PubMed2003

The role of visuospatial attention in developmental dyslexia: evidence from a rehabilitation study.

Shifting of visual attention induced by peripheral cues was studied in 24 children with specific reading disorder (SRD) or dyslexia and was compared with that of 19 normal readers by means of a covert orienting paradigm. This paradigm presents participants with valid, neutral and invalid spatial cues preceding the presentation of a target stimulus. As compared to normal readers, in SRD children the inhibition effect (i.e. the difference between neutral and invalid cues) was absent. The 24 SRD children were divided into two groups matched for age, IQ and reading ability to study the efficacy of two different rehabilitation procedures. We assessed the effects on reading accuracy and speed over a 4-month treatment with visual hemisphere specific stimulation (VHSS; J. Learn Disabil. 25 (1992) 102) vs. traditional speech training. The VHSS program trains participants to perform rapid endogenous attentional orienting by presenting briefly flashed words in the peripheral visual field. We found that children treated with VHSS showed significant changes in their attentional inhibition process, as indicated by increased costs for 'reorienting' the attentional focus. As this treatment program also proved to be highly efficient in improving the children's reading abilities, the possible causal relationship between reading and inhibition mechanisms of visuospatial attention was discussed.

Attention↗
PubMed2001

IMRT: high-definition radiation therapy in a community hospital.

A multileaf collimator (MLC)-based intensity-modulated radiation therapy (IMRT) program was implemented successfully at Monmouth Medical Center, a community hospital at Long Branch, New Jersey. Our clinical experience gained in the treatment of over 80 patients using IMRT for prostate, head and neck, and brain is reviewed, and some of the clinical issues are also, discussed. Implementation of the IMRT requires a treatment planning system, computer-controlled beam-shaping aperture, electronic record and verify system, and a good physics quality assurance program. These components, by grouping them efficiently, have created a seamless workflow for our complete radiotherapy process of IMRT. Each of these radiotherapy processes are discussed for clarity and the clinical importance is also evaluated. Of particular interest is inverse treatment planning that will impact treatment delivery such as beam orientation, treatment ports, and organ motion of IMRT. A checklist for physics and departmental quality assurance is suggested, with the intention of providing systematic workflow, making IMRT feasible at a community medical center setting. This is especially important because most of our cancer patients received radiation therapy locally. Lastly, the reimbursement issue affecting the implementation of IMRT at our medical center is also discussed to justify this new treatment protocol for future clinical outcomes.

Head and Neck Neoplasms↗
PubMed1999

The human homologue of Caenorhabditis elegans CED-6 specifically promotes phagocytosis of apoptotic cells.

A key feature of the process of programmed cell death (apoptosis) is the efficiency with which the dying cells are recognized and engulfed by phagocytes [1]. Apoptotic cells are rapidly cleared either by neighbouring cells acting as semi-professional phagocytes or by experts of the macrophage line, so that an inflammatory response is avoided [2]. The Caenorhabditis elegans gene ced-6 is required for efficient engulfment of apoptotic cells [3] and is one of a group of genes that define two partially redundant parallel pathways for the engulfment process [4] [5]. These pathways may be conserved across evolution, as two other engulfment genes have human homologues. A CED-5 homologue is part of a human CrkII-DOCK180-Rac signaling pathway proposed to mediate cytoskeletal reorganization [6] [7] [8] and a CED-7 homologue is similar to the ABC transporters [9] [10]. Here, we report the cloning and characterization of human CED-6, a human homologue of C. elegans CED-6. The 34 kDa hCED-6 protein is expressed in most tissues, some human cancer cells, and in primary human macrophages. We developed an assay that quantitates the phagocytic activity of mammalian macrophages: the number of apoptotic cells that have been internalized is measured by the uptake of lacZ-positive apoptotic cells by adherent transgenic macrophages. The results of this assay demonstrate that overexpression of hCED-6 promotes phagocytosis only of apoptotic cells and suggest that hCED-6 is the mammalian orthologue of C. elegans CED-6 and is a part of a highly conserved pathway that specifically mediates the phagocytosis of apoptotic cells.

Animals↗
PubMed2000

Estimating the microvascular benefits of screening for type 2 diabetes mellitus.

OBJECTIVE: To define the relative benefits of screening for diabetes and improved treatment programs and ways of improving the efficiency of screening for a population-based cohort derived from the Third National Health and Nutrition Examination Survey (NHANES III). METHODS: A Markov decision model is used to estimate microvascular benefits of glucose control for four different screening and treatment scenarios, including either universal screening or improved glucose control of known diabetic subjects, neither, or both. RESULTS: A population cohort of subjects with recent onset of diabetes (< 5 years) was derived from NHANES III (of whom close to half were unaware that they had diabetes). In this population-based cohort, the total benefit achievable by universal screening and improved treatment (limiting HbA1c to less than 9%) is a reduction of about 30,000 cases of blindness over the lifetime of the cohort. Screening alone results in 7% of this benefit, and improved treatment alone provides 65%. Screening a targeted group of patients with three or more risk factors for developing diabetes would reduce the number of required fasting glucose measurements needed by 82% and provide 50% of the total benefit of screening the entire population with a fasting glucose measurement. CONCLUSIONS: Morbidity from type 2 diabetes can be most effectively reduced by developing ways to modestly improve the glycemic control of known diabetic subjects, particularly those with high A1c's and early onset of disease. Targeting can significantly reduce the number of persons who need to be screened with a fasting blood test while preserving a large component of the benefit of screening.

Blindness↗
PubMed2000

Epidoxorubicin and docetaxel as first-line chemotherapy in patients with advanced breast cancer: a multicentric phase I-II study.

BACKGROUND: The combination of anthracyclines and taxanes is currently considered the first choice chemotherapy in advanced breast cancer (ABC) and considerable emphasis has been placed on programs exploring the safest and most efficient way to integrate these classes of drugs in both the metastatic and, more recently, the adjuvant setting. We report here the overall results of the combination of epidoxorubicin (E) 90 mg/m2 and docetaxel (D) 75 mg/m2 as first-line chemotherapy in ABC. PATIENTS AND METHODS: A total of 70 patients were entered in the initial dose-finding study (20 patients) and in the subsequent extended phase II trial (50 patients). Overall 54% of patients had dominant visceral disease and 57% had at least two metastatic sites. Adjuvant anthracyclines were allowed in the phase II part of the study based on the lack of cardiac toxicity observed in the phase I study at a median cumulative E dose of 480 mg/m2. A maximum of eight cycles of the combination was allowed, and cardiac function was monitored at baseline and after every second course by echocardiography. RESULTS: Overall, the median number of cycles administered with the combination was 4 (range 3-8). Neutropenia was confirmed to be the main haematological toxicity, with granulocyte colony-stimulating factor (G-CSF) support required in 44% of the cycles. Febrile neutropenia occurred in 12% of cycles of the combination but 52% of the episodes could be managed on an outpatient basis with oral antibiotics. Overall, the median cumulative dose of E, including prior adjuvant anthracyclines, was 495 mg/m2 (range 270-1020 mg/m2). One patient who received adjuvant E together with radiotherapy to the left chest wall developed fully reversible clinical signs of cardiotoxicity and a significant decrease of LVEF to 35% after a cumulative E dose of 870 mg/m2, with four additional patients (6%) developing asymptomatic and transient decline of resting LVEF. The overall response rate (ORR) in 68 evaluable patients was 66% (95% confidence interval (95% CI): 54%-73%). A comparable antitumour activity of 71% was reported in the group of patients with a prior adjuvant chemotherapy with anthracyclines. After an overall median follow-up time of 22 months (range 4-39+), the median time to progression (TTP) was 4.5 months and the median duration of response was 8 months (range 3-16). No pharmacokinetic (Pk) interaction could be demonstrated between E and D when given simultaneously and sequentially with a one-hour interval. CONCLUSIONS: The combination of E and D in a multiinstitutional setting is an active and safe regimen in poor-prognosis patients with ABC. New combinations and schedules are worth considering in an attempt to further improve disease response and long-term control of the disease.

Adult↗
PubMed2002

Resource allocation to prevent trachomatous low vision among older individuals in rural areas of less developed countries.

Trachomatous low vision can be prevented by treating or preventing infection or through surgery to treat trichiasis. Resource allocation to prevent trachomatous low vision should be directed to those interventions that are the most cost-effective. In order to assess which of many potential interventions are the more cost-effective, data on the epidemiology of the disease, the effectiveness of community- and facility-based interventions, and the cost of the interventions are required. This paper provides a stylized model of the path from risk of infection through disease to trachomatous low vision or blindness that delineates the points at which interventions may occur and for which data are required. The literature reveals a considerable amount of data regarding the epidemiology of the trachoma and its sequelae but little on the effectiveness of community-based interventions and only one study that measured costs directly. More data are needed to assist policy makers and international program partners who seek to make efficient resource allocation decisions in an effort to eliminate trachoma as a cause of incident blindness in the developing countries in which trachomatous blindness remains prevalent.

Anti-Bacterial Agents↗
PubMed2002

Identifying patients with gastroesophageal reflux disease: validation of a practical screening tool.

A reliable, accurate noninvasive method for identifying patients with gastroesophageal reflux disease (GERD) in the primary care setting is needed. A population-based case-finding instrument may assist managed care organizations in identifying candidates for disease management or quality improvement programs. Our aim was to develop and validate a GERD case-finding instrument. A 12-item "GERD Screener" was developed based on literature review and expert opinion with questions about heartburn and regurgitation frequency and severity and medication use, as well demographics and exclusion criteria. Categorical and continuous scoring methods with and without medication use were developed a priori. Using a telephone interview in a medical group, we identified and enrolled 100 subjects with a history of GERD-like symptoms and 103 controls. Each subject completed the GERD Screener, a validated gastrointestinal symptom questionnaire, the Digestive Health Symptom Index (DHSI), and was evaluated independently by two gastroenterologists using a structured format. Agreement by the two physicians that symptoms were consistent with GERD and required an intervention was considered the gold standard. In all, 70 subjects were classified as having GERD and 106 as controls using the gold standard (K = 0.73; 95% CI, 0.63-0.82). The scoring method for the screening instrument using a continuous measure of GERD symptoms (frequency and severity) and weighted medication use resulted in an area under ROC of 0.89 (95% CI, 0.84-0.94). Using a cutoff of >9 points, this measure was 83% sensitive and 83% specific. Compared to the gold standard, the DHSI GERD subscale has an area under ROC of 0.89 (95% CI, 0.84-0.94). The GERD Screener was highly correlated with the DHSI GERD subscale, r = 0.78 (95% CI 0.72-0.83; P < 0.0001). In conclusion, the GERD Screener has demonstrated construct, convergent, and predictive validity. It is shorter than existing validated instruments, practical, and easily administered, which may reduce the response and administrative burden. This may serve as a valuable case-finding instrument in primary-care and managed-care organizations wishing to implement programs to improve the quality and efficiency of care.

Gastroesophageal Reflux↗
PubMed2002

Activation of metalloproteinases and their association with integrins: an auxiliary apoptotic pathway in human endothelial cells.

Anchorage of cells to the extracellular matrix and integrin-mediated signals play crucial roles in cell survival. We have previously shown that during growth factor deprivation-induced apoptosis in human umbilical vein endothelial cells (HUVECs), key molecules in focal adhesions and adherens junctions are cleaved by caspases. In this study we provide evidence for a selective upregulation of cell-associated matrix metalloproteinases (MMPs). We observe a physical association of MMP2 with beta1 and alphav integrins, which increased three- to fourfold during apoptosis and is dependent upon integrin beta1 levels and activation state. Both enforced activation of beta1 integrin by a specific antibody and inhibition of MMPs protect HUVECs from apoptosis. We hypothesize that, prior to the commitment to apoptosis, 'inside-out' signals initiated by the apoptotic stimulus alter cell shape together with the activation states and/or the availability of integrins, which promote matrix-degrading activity around dying cells. This 'auxiliary' apoptotic pathway may interrupt ECM-mediated survival signaling, and thus accelerate the efficient execution of the cell death program.

Apoptosis↗
PubMedDate not supplied

Effect of rabbit line on a program of cryopreserved embryos by vitrification.

The aim of this study was to assess the application of a cryopreservation program to preserve two selected rabbit lines. One of them was selected by litter size at weaning, line V (Synthetic breed). The second, line R (synthetic breed), was selected by growth rate. In this study, embryos were collected, from donor does belonging to the 7th and 15th generations of lines R and V, respectively, were vitrified and were stored from 1992-1993. Those embryos from donor does belonging to the 17th and 21st generations of lines R and V respectively, were vitrified and sotred from 1998-1999. Embryo transfers were carried out in 1999. Morphologically normal embryos at the morulae stage were cryopreserved by vitrification in a 2.8 M dimethyl-sulfoxide + 3.5 M ethylene-glycol + 0.3 g x L(-1) bovine serum albumine in Dulbecco phosphate buffered saline solution. The main problem in the cryopreservation program was the low embryo production efficiency: significant differences were obtained in recovery efficiency between lines and line R showed the lowest proportion of donor does with 55% (at least 4 normal embryos) vs. 72% in line V. However, after transfer in recipient does of line V, the fertility rate at birth (81%), the rate of alive born by pregnant recipients (43%) and the number of males and does with offspring (9 to 18 different males, 12 to 32 females) enabled the different generations from each line to be re-established and studies on the selection process genetic gain to be developed.

Animals↗
PubMed1997

[Electromyography-controlled muscle rehabilitation--knee injuries].

Surface is a noninvasive, mostly nonreactive, objective measuring procedure for evaluation of the degree of muscle activation. It allows for accurate assessments of the neuromuscular system and description of adaptations resulting from injury. Decreases in torque, EMG amplitude and EMG frequency occur as a result of knee joint injuries. Efficiency checks and evaluations of training programs and neuromuscular treatment can be done. Decreases in torque, EMG amplitude and EMG frequency found after knee joint injury (cruciate ligament, meniscus) are due to intraarticular and periarticular afferent processes. 12 weeks postoperatively, the neuromuscular deficits from cruciate ligament injury have increased. While complete recovery can be achieved following meniscus fixation (more than 1 year postoperatively), cruciate ligament injuries lead to chronically reduced EMG median frequencies.

Athletic Injuries↗
PubMed1985

[Myopia: causes and prevention].

Myopia is the most common disorder of visual function in many literate populations, affecting 70% of some specific groups. The causes may lie in genetic or environmental factors. This article discusses the arguments put forward to support of the biological and environmental theories of the cause of myopia. It is argued that the biological theory has never been proven empirically and that the evidence clearly points to the role of close-range work in the prevalence of myopia as a massdisease. Primary prevention is difficult in this situation and compensatory strategies (relaxation, eye exercises) are rather ineffective. Prevention strategies are discussed and a research program to evaluate their effectiveness and efficiency is proposed.

Accommodation, Ocular↗
PubMed2005

Framework for kernel regularization with application to protein clustering.

We develop and apply a previously undescribed framework that is designed to extract information in the form of a positive definite kernel matrix from possibly crude, noisy, incomplete, inconsistent dissimilarity information between pairs of objects, obtainable in a variety of contexts. Any positive definite kernel defines a consistent set of distances, and the fitted kernel provides a set of coordinates in Euclidean space that attempts to respect the information available while controlling for complexity of the kernel. The resulting set of coordinates is highly appropriate for visualization and as input to classification and clustering algorithms. The framework is formulated in terms of a class of optimization problems that can be solved efficiently by using modern convex cone programming software. The power of the method is illustrated in the context of protein clustering based on primary sequence data. An application to the globin family of proteins resulted in a readily visualizable 3D sequence space of globins, where several subfamilies and subgroupings consistent with the literature were easily identifiable.

Algorithms↗