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PubMed2002

Human IgG monoclonal anti-alpha(IIb)beta(3)-binding fragments derived from immunized donors using phage display.

Previous studies of the immune response in polytransfused Glanzmann thrombasthenia (GT) patients and in autoimmune thrombocytopenic purpura (AITP) have relied on serum analysis and have shown the frequent development of Abs directed against the alpha(IIb)beta(3) integrin. However, little is known about the molecular diversity of the humoral immune response to alpha(IIb)beta(3) due to the paucity of mAbs issuing from these pathologies. We have isolated human IgG anti-alpha(IIb)beta(3) binding fragments using combinatorial libraries of single-chain IgG created from the B cells of a GT and an AITP patient, both with serum Abs. Ab screening was performed using activated platelets or activated alpha(IIb)beta(3)-expressing Chinese hamster ovary cells. Sequencing of selected phage Abs showed that a broad selection of genes from virtually all V gene families had been used, indicating the diversity of the immune response. About one-half of the V(H) and V(L) segments of our IgG anti-alpha(IIb)beta(3) fragments displayed extensive hypermutations in the complementarity-determining region, supporting the idea that an Ag-driven immune response was occurring in both patients. The H chain complementarity-determining region 3 analysis of phage Abs revealed motifs other than the well-known RGD and KQAGDV integrin-binding sequences. To our knowledge, our study is the first to illustrate multiple human IgG anti-alpha(IIb)beta(3) reactivities and structural variations linked to the anti-platelet human immune response. Human alpha(IIb)beta(3) Abs preferentially directed against the activated form of the integrin were further characterized because platelet alpha(IIb)beta(3) inhibitors are potential therapeutic reagents for treating acute coronary syndromes. Currently available alpha(IIb)beta(3) antagonists do not specifically recognize the activated form of the integrin.

Aged↗
PubMed2003

[The small epidemiologic transition: further decrease in infant mortality due to medical intervention during pregnancy and childbirth, yet no decrease in childhood disabilities].

The small epidemiologic transition, which started to occur during the 1960s, was a continuation of the large epidemiologic transition. The large epidemiologic transition concerned a strong increase in the life expectancy as a result of the virtual disappearance of mortality during the early life years. During the most recent stage of this epidemiologic transition, two types of medical intervention in pregnancy and childbirth were introduced: antenatal screening and diagnosis followed by selective abortion, and neonatal intensive care for preterm babies. These two types of intervention have opposite epidemiologic effects. On the one hand these have led to a further decrease in the mortality. Yet, on the other hand the prevalence of childhood disabilities has scarcely decreased or has not decreased at all, because intensive interventions after childbirth can lead to more disabilities occurring in the population than those removed due to selective abortion. The small epidemiologic transition has arisen from an expansion in knowledge and possibilities to observe and intervene. These have indeed led to an increase in options before, during and after pregnancy, but not to a reduced morbidity at the start of life.

Child↗
PubMed2006

Virtual reality training for stroke rehabilitation.

OBJECTIVE: To evaluate the effectiveness of a 2-D virtual reality (2DVR) programme in the training of people with stroke on how to access and use the station facilities of the Mass Transit Railway (MTR). METHOD: A flat-screen 2DVR based training programme and a corresponding, typical psycho-educational programme with video modelling were developed for comparison through a research design that involved a randomised control group pre-test and post-test. RESULTS: Twenty and sixteen subjects respectively received 10 training sessions using the 2DVR strategy and a video-based psycho-educational programme. An additional 22 subjects formed the control group. They were assessed by using a behavioural checklist of MTR skills and a newly validated MTR self-efficacy scale. The subjects of both training groups showed a significant improvement in their knowledge, skills and self-efficacy in using the MTR (p<0.01), whereas, the MTR skills and self-efficacy of the control group remained stable over a four-week interval. CONCLUSION: Though both training programmes were effective in training the patients with stroke, they demonstrated differential improvements in MTR skills and related self-efficacy. Additional studies are recommended to identify the most effective training procedures for maintaining these skills and the best transfer ratio in the training of VR-based community living skills of people with stroke.

Aged↗
PubMed1990

Screening for cervical cancer in emergency centers and sexually transmitted disease clinics.

Low-income women are at increased risk of developing cervical cancer compared with middle- and upper-income women. How can poor women be reached for screening and early diagnosis of cervical cancer and its precursor stages? One answer to this question is based on the observation that a high percentage of the unscreened population has received some form of medical care within the previous 5 years. Emergency centers and sexually transmitted disease (STD) clinics often provide such care to patients who lack a regular source of health care. Thus, they represent potential resources for cervical cancer screening. However, in a survey of 19 hospitals whose patient populations include a high proportion of low-income patients, only five reported a protocol for cervical cancer screening in their emergency centers. Similarly, all 11 STD clinics included in this survey reported that fewer than 5% of their female patients had a Papanicolaou smear taken even though virtually all of them received a pelvic examination. Based on these findings, it appears that health care administrators and policymakers could intensify their cancer prevention programs by mobilizing these resources for cancer control.

Community Health Centers↗
PubMed1977

Gasoline sniffing and tetraethyl lead poisoning in children.

Two cases of acute organic lead poisoning following gasoline sniffing, with one death, are reported. Signs of lead encephalopathy with elevated blood lead levels and markedly decreased levels of erythrocytic delta-amino levulinic dehydratase (ALAD) were demonstrated. Erythrocytic ALAD activity was used as a screening test for the detection of tetraethyl lead (TEL) poisoning in a group of 43 children who were presumed gasoline sniffers. Their mean ALAD activity was 190 units compared to a mean of 538 units for a control group. A survey of schoolchildren in another isolated community revealed that 59% had decreased ALAD activity, which correlated well with a history of gasoline sniffing. Only 5% of the children had blood lead levels over 40 microgram/dl. The two surveys herein reported suggest that there may be large numbers of children living in isolated communities who are suffering from TEL poisoning as a result of gasoline sniffing. This constitutes a major medical, public health, and social problem heretofore virtually unrecognized.

Adolescent↗
PubMed1993

Comprehensive screening of the human KRAS2 gene for sequence variants.

To search for mutations in the human KRAS2 oncogene, we have analyzed polymerase chain reaction (PCR) fragments by denaturing gradient gel electrophoresis. We used six different PCR fragments to screen the five coding exons of this gene as well as the splice sites. GC clamps were added to each fragment by means of heteroduplex extension. We infer, from a theoretical analysis in which we employed the computer programs MELT and SQHTX, that virtually any mutation affecting one or a few base pairs in the coding exons or splice sites will be detectable. Thus the system that we describe should allow comprehensive detection of mutations throughout the coding exons and splice sites of the KRAS2 gene. As an example, we show that missense mutations at codons 12, 13, and 61 can be detected; mutant KRAS2 gene isolated from human tumors have been found to contain mutations only at these codons. We also report the discovery of three new polymorphic loci in the KRAS2 gene. We show that PCR reactions containing two or three fragments can be screened in a single lane of a denaturing gradient gel; this dramatically increases the number of base pairs that can be screened per gel.

Base Sequence↗
PubMed1989

Effect of developer temperature changes on the sensitometric properties of direct exposure and screen-film imaging systems.

A heat exchanger was developed and incorporated into the recirculation system of a dental processor to maintain strict temperature control. Without the heat exchanger, developer temperature rose steadily over 8 h to a maximum of 35.7 degrees C: with the heat exchanger it was maintained, regardless of ambient conditions, at the desired temperature with virtually no fluctuation. Sensitometric properties of base and fog, speed, and average gradient were measured for D and E speed films and Lanex Regular/T-Mat G and Lanex Fast/T-Mat Hscreen-film systems at developer temperatures of 21.1, 23.8, 26.7, 29.4 and 32.2 degrees C. Small changes in these properties were found for D and E speed films: on the other hand, Lanex Regular/T-Mat G showed a 65% increase in base and fog and Lanex Fast/T-Mat H a 43% increase in average gradient over the temperature range studied. Although these changes may not be clinically significant for intra-oral and dental radiography, the variations in image quality may compromise controlled imaging experiments and clinically compromise radiographic quality when using screen-film systems.

Radiography, Dental↗
PubMed2004

Benefits and costs of interventions to improve breast cancer outcomes in African American women.

PURPOSE: Historically, African American women have experienced higher breast cancer mortality than white women, despite lower incidence. Our objective was to evaluate whether costs of increasing rates of screening or application of intensive treatment will be off-set by survival benefits for African American women. METHODS: We use a stochastic simulation model of the natural history of breast cancer to evaluate the incremental societal costs and benefits of status quo versus targeted biennial screening or treatment improvements among African Americans 40 years of age and older. Main outcome measures were number of mammograms, stage, all-cause mortality, and discounted costs per life year saved (LYS). RESULTS: At the current screening rate of 76%, there is little incremental benefit associated with further increasing screening, and the costs are high: 124,053 US dollars and 124,217 US dollars per LYS for lay health worker and patient reminder interventions, respectively, compared with the status quo. Using reminders would cost 51,537 US dollars per LYS if targeted to virtually unscreened women or 78,130 US dollars per LYS if targeted to women with a two-fold increase in baseline risk. If all patients received the most intensive treatment recommended, costs increase but deaths decrease, for a cost of 52,678 US dollars per LYS. Investments of up to 6,000 US dollars per breast cancer patient could be used to enhance treatment and still yield cost-effectiveness ratios of less than 75,000 US dollars per LYS. CONCLUSION: Except in pockets of unscreened or high-risk women, further investments in interventions to increase screening are unlikely to be an efficient use of resources. Ensuring that African American women receive intensive treatment seems to be the most cost-effective approach to decreasing the disproportionate mortality experienced by this population.

Adult↗
PubMed2006

Pathological characteristics of prostate cancer detected through prostate specific antigen based screening.

PURPOSE: Since the introduction of PSA testing for CaP, there has been an increase in CaP detection. However, it is uncertain to what extent clinically insignificant tumors are being diagnosed and treated. In a large, community based population we determined the pathological characteristics of screening detected cancers. MATERIALS AND METHODS: From 1989 to 2001, 35,661 men were enrolled in a longitudinal prostate cancer screening study. Data were available on 3,492 of the 3,568 men (98%) diagnosed with CaP during this study period. Radical prostatectomy was performed in 2,254 men (63%). Clinical stage, Gleason score and pathological analysis were recorded and analyzed in the context of preoperative PSA, digital rectal examination findings, PSA velocity and the year of cancer detection. RESULTS: CaP was detected in 10% of men. Virtually all cases were clinically localized (99.8%) and approximately 70% treated with radical prostatectomy were pathologically organ confined disease. Fewer than 10% of tumors would be considered clinically insignificant based on 2 previously published pathological criteria. CONCLUSIONS: Compared to the high prevalence of CaP found in autopsy studies there is a lower detection rate using current screening protocols. Although the outcomes are unknown if these tumors had been left untreated, the majority met pathological criteria for significant cancer.

Adult↗
PubMed1989

Present status of serum markers.

Tumor markers presently in use generally meet only one or two of the criteria for the ideal marker, which are: tumor specificity, correlation with tumor bulk and stage of the disease, decrease to normal after successful treatment, and rise prior to clinical manifestations of recurrence. In addition, virtually all are elevated in some benign conditions. Currently their greatest usefulness is for confirmation of clinical suspicion and for monitoring known disease. Some tumor markers which are not effective as screening tests can be used to evaluate the patient's response to therapy. The discovery of oncogenes holds great promise for a new generation of tumor markers. Major breakthroughs in the fields of molecular biology and tumor immunology seem imminent with eventual application possibly in the treatment of cancer.

Antigens↗
PubMed1992

A new computer program for detailed off-line analysis of swimming navigation in the Morris water maze.

The program TRACK-ANALYZER runs on AT-compatible microcomputers and performs off-line analysis of data recorded from Morris water-maze experiments by means of a video tracking system or digitizing tablet. Raw data must be available on disk as ASCII-files listing position coordinates sampled at a constant frequency. Automatic recognition and correction of artifacts and missing data is a key feature of the program, as well as the option to combine commands to user-defined macros. TRACK-ANALYZER offers maximal flexibility regarding experimental schedule, maze geometry and recording parameters and may also be used to analyze open-field activity. In addition to calculating basic parameters of the swim path, such as path length and time, the program counts crossings and hits of goal platform and four virtual reference annuli, calculates search times in five different maze fields, determines directionality, tortuosity and turning preferences of swimming behavior and allows the viewing of any number of trials simultaneously on screen. ASCII-formated data output may easily be exported to commercial statistics and graphics software.

Animals↗
PubMed1997

Isolation, characterization and molecular cloning of the mannose-binding lectins from leaves and roots of garlic (Allium sativum L.).

Two novel lectins were isolated from roots and leaves of garlic. Characterization of the purified proteins indicated that the leaf lectin ASAL is a dimer of two identical subunits of 12 kDa, which closely resembles the leaf lectins from onion, leek and shallot with respect to its molecular structure and agglutination activity. In contrast, the root lectin ASARI, which is a dimer of subunits of 15 kDa, strongly differs from the leaf lectin with respect to its agglutination activity. cDNA cloning of the leaf and root lectins revealed that the deduced amino acid sequences of ASAL and ASARI are virtually identical. Since both lectins have identical N-terminal sequences the larger Mr of the ASARI subunits implies that the root lectin has an extra sequence at its C-terminus. These results not only demonstrate that virtually identical precursor polypeptides are differently processed at their C-terminus in roots and leaves but also indicate that differential processing yields mature lectins with strongly different biological activities. Further screening of the cDNA library for garlic roots also yielded a cDNA clone encoding a protein composed of two tandemly arrayed lectin domains. Since the presumed two-domain root lectin has not been isolated yet, its possible relationship to the previously described two-domain bulb lectin could not be studied at the protein level.

Amino Acid Sequence↗
PubMed2000

Allergic bronchopulmonary aspergillosis in the asthma clinic. A prospective evaluation of CT in the diagnostic algorithm.

OBJECTIVE: Allergic bronchopulmonary aspergillosis (ABPA) occurs in cases of atopic asthma and may result in important lung disease. Early diagnosis is essential as this disease is responsive to steroids. However, while asthma is common, ABPA is infrequently diagnosed. CT allows precision in the diagnosis of central bronchiectasis (which is virtually pathognomonic of ABPA) and may enable earlier diagnosis. DESIGN: A prospective evaluation of 255 patients with asthma for ABPA, using skin prick testing (SPT) for Aspergillus fumigatus (AF) as a screening tool and incorporating CT into the diagnostic algorithm. SETTING: Asthma clinic, Green Lane Hospital, Auckland, New Zealand. PARTICIPANTS: Patients with asthma. INTERVENTIONS: ABPA was diagnosed using "essential" criteria (ie, asthma, SPT positivity to AF, elevated serum total IgE, elevated serum AF-specific IgE, and pulmonary infiltrates seen on chest radiography or central bronchiectasis seen on CT scan) and "minimal essential" criteria (ie, asthma, SPT positivity, and central bronchiectasis). MEASUREMENTS AND RESULTS: Two hundred fifty-five consecutive patients with asthma who consented to SPT were studied: 218 of 255 patients (86.8%) were atopic; and 47 of 255 patients (21.6%) were AF-positive, of whom 35 accepted further evaluation including CT scanning. A secure diagnosis of ABPA, satisfying all essential criteria, was evident in 9 of 35 patients (25.7%), a proportion that increased to 13 of 35 patients (37.1%) by using the minimal essential diagnostic criteria. CONCLUSIONS: SPT positivity to AF was present in approximately 20% of patients in the asthma clinic. A diagnosis of ABPA is disclosed by CT in 25 to 40% of SPT-positive patients, depending on the selection of diagnostic criteria. These findings support the use of SPT as a screening tool in the asthma clinic and indicate that a routine CT scan is warranted in SPT-positive patients.

Adult↗
PubMed2005

Panoramic views for virtual endoscopy.

This paper describes a panoramic projection designed to increase the surface visibility during virtual endoscopies. The proposed projection renders five faces of a cubic viewing space into the plane in a continuous fashion. Using this real-time and interactive visualization technique as a screening method for colon cancer could lead to significantly shorter evaluation time. It avoids having to fly through the colon in both directions and prevents the occlusion of potential polyps behind haustral folds.

Algorithms↗
PubMed1983

Incidence of neural tube defects in liveborn and stillborn infants in British Columbia over a 10-year period.

Reports of an apparent decline in the incidence of neural tube defects (NTDs) have come from various parts of the world. If these findings are consistent they would have an important impact on prenatal diagnosis and on screening programs. The incidence of NTDs over a 10-year period was examined in British Columbia, a province that has a population-based health surveillance registry through which there is virtually complete ascertainment of liveborn infants with NTDs. The results showed a significant decrease in incidence only for stillborn infants with anencephaly. The increased use of ultrasonography and the subsequent termination of pregnancies in which the fetus has been found to have anencephaly may explain this observation.

Anencephaly↗
PubMedDate not supplied

[Gastric cancer: diagnostic problems].

Gastric cancer is still one of the most prevalent cancer diseases. Despite a more than 30-year priority use of endoscopy in the diagnosis of gastric cancer, this condition is still virtually impossible to be detected at early stages. Many-year experience gained by the authors permitted them formulate two causes of this rather poor state of the art: 1) no screening programs for the early detection of gastric cancer and 2) under-valuation of the frequency of endophytic (infiltrative) forms of gastric tumors and of potentialities of modern x-ray examination in the diagnosis thereof. According to their results, gastric cancer was diagnosed in 539 cases out of more than 40,000 screenings. Analysis of more than 2,000 common clinical cases of gastric cancer brought the authors to a conclusion that endophytic, infiltrative (intraparietal) form of malignant tumor growth is the major form. A new sign of initial manifestations of intraparietal gastric cancer is suggested: intraparietal blastomatous infiltration symptom. The authors emphasize that roentgenology should again become the principal method in the diagnosis of gastric cancer. Only combined use of roentgenology and endoscopy may appreciably improve the detection rate of this grave disease.

Diagnosis, Differential↗
PubMed1999

Highly sensitive micro-plate enzyme immunoassay screening and NCI-GC-MS confirmation of flunitrazepam and its major metabolite 7-aminoflunitrazepam in hair.

Flunitrazepam (Rohypnol) is a benzodiazepine used in the treatment of insomnia as a sedative hypnotic and as preanesthetic medication in European countries and Mexico. Although it has no medicinal purpose in the United States, the occurrence of its abuse is increasing. Sexual abuse of both men and women while under the influence of so-called "date-rape" drugs has been the focus of many investigations. Reported date-rape drugs include flunitrazepam (FN), clonazepam, diazepam, oxazepam, gamma-hydroxybutyrate, and many others. FN has been banned in the United States because of its alleged use in such situations. Unfortunately, the detection of FN or its metabolites 7-aminoflunitrazepam (7-AFN) and desmethylflunitrazepam in a single specimen such as urine or blood is difficult in criminal situations because of the likelihood of single-dose ingestion and the length of time since the alleged incident. Hair provides a solution to the second of these problems in that drugs tend to incorporate into hair and remain there for longer periods of time than either urine or blood. There are various techniques for the detection of FN in plasma, blood, and urine, but little work has been done with hair. Hair collection is a virtually noninvasive procedure that can supply information on drug use for several months preceding collection. The objective of this paper was to determine if a commercially available micro-plate enzyme immunoassay system was sufficiently sensitive for the routine screening of 7-AFN in hair by the development of extraction procedures and optimization of the immunoassay kit. Further, this study used the same solid-phase extraction to isolate FN and its major metabolite, 7-AFN, and gas chromatography-mass spectrometry with negative ion chemical ionization for confirmation. Two seven-point standard curves were established ranging from 0.5 pg/mg to 100 pg/mg for 7-AFN and 2.5 pg/mg to 200 pg/mg for FN with respective deuterated internal standards. A replicate analysis of controls was performed to establish inter- and intraday variabilities. Two suicide cases along with one alleged date-rape case and one case of an emergency room patient whose blood screened positive for benzodiazepines were analyzed. All the hair specimens screened positive for benzodiazepines using micro-plate enzyme immunoassay. Two cases, including the date-rape case, were negative for FN and 7-AFN, and two postmortem hair samples were confirmed positive for FN and its metabolite.

Anti-Anxiety Agents↗