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PubMed1999

Pace of leprosy elimination and support teams in Bihar state, India.

Despite the extensive implementation of multiple drug therapy (MDT) in most leprosy-endemic countries world-wide since 1982, bringing about a remarkable reduction in prevalence, there are still regions at the sub-national level where the implementation of MDT remains difficult. The state of Bihar (population 86.3 million) in India is a good example of such a region. Previously rated as one of the most highly endemic states, it still contributes about 21% of the total caseload in India and about 12% of the global caseload. For various reasons, case-finding and drug treatment have lagged behind the progress made in most other states in the country and in 1996, the Damien Foundation India Trust (DFIT) volunteered technical support to increase the pace of elimination. Sixteen out of the 39 districts in the state were allocated, with a population of 41.8 million. Support teams, including a Medical Advisor and a Non-Medical Supervisor, both with over 10 years experience of leprosy work and control programmes, were provided to assist and work alongside government staff in case detection, treatment delivery, case-holding and discharge in their respective areas of operation. New case detection by intensive survey increased by 394% and total new case detection by 226% during the year 1996-1997, with similar trends in the following year. Striking improvements were also observed in MDT coverage, treatment regularity, monitoring and discharge of patients and in the training of local staff. This collaboration between a non-government agency (DFIT) and the staff of the National Leprosy Eradication Programme in 16 out of 39 districts in the State of Bihar has clearly been extremely successful. Similar approaches in the remaining districts of Bihar, and in other parts of India, where the infrastructure is available but inadequate, may contribute significantly to achieving the elimination goal at national and sub-national levels.

Drug Therapy, Combination↗

PubMed2000

[Update on gastroenterology].

In the field of mass detection of colorectal cancer by Hemoccul test, the results of the Burgundy study confirm the two european studies previously published and encourage to extend this training to the whole country. In oncogenetic field, a recent publication suggest some different clinical criteria that Amsterdam criteria to define a Lynch syndrome. When genetic markers are performed in a population selected according to these type I criteria, HNPCC mutation could be detected in 28% of cases. In colorectal cancer surgery, the debate remains open on the place of coeliosurgery. A recent published series of 135 colon cancers operated by coeliosurgery do not show any recurrence on trocar orifices. A US study has confirmed the prognostic value of the number of lymph nodes analyzed after resection of colorectal cancer. In adjuvant treatment of stage II colon cancer, two contradictory publications have been reported in the Journal of Clinical Oncology. However, the results of the Impact B2 Group are more consistent and support the fact that chemotherapy cannot be recommended as a standard treatment in state II colon cancer. The actualities in the liver metastases focused on the new local destruction technics that are cryosurgery and radiofrequency. Concerning the chemotherapy of metastatic colorectal cancer, important results have been published in second line therapy showing the superiority of Campto compared to best supportive care or 5FU based chemotherapy both in term of overall survival and quality of life. In first line chemotherapy, the superiority of bi-therapies (LV5FU2 and oxaliplatin or LV5FU2 and irinotecan) has been confirmed compared to LV5FU2 alone. A recent publication showed that patients older than 70 years tolerate chemotherapy for colorectal cancer as well as younger patients with the same efficacy. In esophagus carcinoma, the most important study didn't show any efficacy of neoadjuvant chemotherapy by 5FU-cisplatin in operable adenocarcinoma of squamous carcinoma of esophagus. The final results of dutch's study in node dissection for gastric cancer do not find any benefit in overall survival comparing D2 versus D1 dissection with a substantial increase in morbidity and mortality in the D2 arm, specially when splenopancreatectomy was performed. Finally, an important study has confirmed the value of per echoendoscopy biopsies for the diagnosis of positive lymph nodes and pancreatic tumors.

Antineoplastic Agents↗

PubMed2001

Comparison of image quality indicators among mammography facilities in Ontario.

OBJECTIVE: To compare the technical aspects of image quality of mammography machines in facilities across Ontario. METHODS: Eight mammographic physics consultants took measurements and calculated accreditation phantom scores, mean glandular dose, entrance exposure, average optical density, half value layer and the limiting resolution of the imaging chain for 100 mammography machines across Ontario. RESULTS: Of the 100 machines, 39 were affiliated with the Ontario Breast Screening Program (OBSP), and the remaining 61 were applying to become OBSP affiliates. All of the OBSP facilities and 32 of the applicants were accredited with the Mammography Accreditation Program (MAP) of the Canadian Association of Radiologists (CAR). All OBSP facilities had passing phantom scores, and 84% of the applicants with CAR accreditation and 79% of those without had passing phantom scores. The mean glandular dose was 1.5 (range 1.0-1.9, standard deviation [SD] 0.22) mGy for OBSP facilities, 1.3 (0.8-1.8, SD 0.29) mGy for CAR accredited and 1.4 (0.9-1.9, SD 0.24) mGy for nonaccredited applicants. Mean entrance exposures were 798 (540-1280, SD 135) mR, 717 (430-980, SD 153) mR and 770 (520-930, SD 116) mR for the OBSP, accredited and nonaccredited facilities respectively. There were no appreciable differences in the mean optical densities (approx. 1.62 OD), mean half-value layers (approx. 0.34 mm Al) or mean resolutions measured with the large focal spot (nominal size of 0.3 mm) either parallel (approx. 16 line pairs/mm) or perpendicular (approx. 14 line pairs/mm) to the cathode-anode axis of the x-ray tube, among the 3 types of facilities. CONCLUSION: Image quality is increased and variability is decreased in facilities participating in a province-wide screening program.

Accreditation↗

PubMed1989

Epidemiology of human papillomavirus (HPV) infections and their associations with genital squamous cell cancer. Review article.

Reliable assessment of the epidemiology of genital HPV infections is hamphered by a number of technical problems. Because of the lack of tissue-culture systems, methods based on morphological approaches (colposcopy, cytology and histopathology) play a central role in HPV diagnosis. Even DNA-hybridization techniques and the recently introduced DNA amplification with PCR are extremely difficult to standardize, and are thus subject to major interlaboratory variation. Further confusion in the field is created by the complex biological behaviour of HPV infections. As established by the long-term prospective follow-up study of over 500 women which has been running in Kuopio since 1981, clinical progression and regression are significantly related to the grade of the lesion at the time of diagnosis (p less than 0.00001, and p = 0.0005, respectively), as well as to the type of HPV (p = 0.0012). Most importantly, however, genital HPV infections seem to run an extremely fluctuating course, passage from manifest to subclinical or latent infection being frequently encountered in individual patients when examined at 6-month intervals over prolonged periods. This explains the significantly divergent prevalence figures reported in different series (ranging from 2% to 80%), which are completely dependent on the technique used to analyse the presence of HPV, i.e. whether a) PAP smear, b) biopsy, c) DNA hybridization, or d) PCR amplification. The first two are capable of disclosing only manifest (clinical) infections, the latter two also the latent ones. In an unselected population of 22-year-old Finnish females, the prevalence of clinical HPV infections was about 3 per cent, and the adjusted annual incidence was 8.0 per cent. According to estimates of the life-time risk, up to 79% of Finnish females will contract at least one HPV infection between the ages 20 to 79 years. When related to the long-term trends in invasive cervical cancer in Finland, it is evident that this 79% life-time risk of becoming HPV-infected or even the observed 15% clinical progression rate for HPV infections in the prospective follow-up study by no means signifies an identical risk of developing cervical cancer (i.e. 0.79 x 0.15 = 11%). It seems likely that in countries where mass-screening programmes exist (and precancer lesions are traced), the high prevalence of HPV infections is not necessarily reflected as an increased prevalence of invasive cervical carcinomas. The distinction of lesions at risk for malignant transformation from those regressing spontaneously will have major implications in therapeutic considerations of genital HPV infections.

Carcinoma, Squamous Cell↗

PubMed2000

Detection of anti-nuclear antibodies from filter paper blood clots using indirect immunoenzyme technique: preliminary experience and results.

BACKGROUND: The facilities to detect antinuclear antibodies (ANA) patterns in patients with systemic rheumatic diseases/connective tissue disorders (CTD) using indirect immunofluorescence (IIF) technique (the gold standard) are sparse; the technique is technically difficult and expensive. A simpler technique, such as the indirect immunoenzyme (IIE) which uses light microscopy, ought to be evaluated for widespread use in our setting. OBJECTIVE: To study the feasibility and relevance of IIE in demonstrating ANA patterns, both from serum and filter paper blood clots (FPBC), in patients with CTD. METHODS: In this pilot study, ANA were detected from sera and FPBC of 21 patients with proven CTD using IIE; paired FPBC and serum samples were simultaneously collected in 10 patients. All samples, coded randomly, were tested by IIE and IIF, along with positive and negative controls. RESULTS: Using IIE, the results of the ANA patterns obtained from FPBC eluates and sera were similar; homogenous (SLE-6, PSS-1, RA-4), speckled (SLE-8, PSS-2, Overlap CTD-1) and centromere (PSS-1). Four SLE patients showed mixed pattern; sensitivity of IIE for lupus was hundred percent. On comparing the results with the serum IIF, the Kappa statistic of agreement was 1 (perfect) and 0.4 (fair) for FPBC-IIF and FPBC-IIE respectively; the results matched between serum IIF and FPBC-IIE in 8 of the 10 paired samples tested. CONCLUSIONS: IIE can demonstrate ANA both from sera and FPBC. This pilot study besides demonstrating positive trends for further probe also creates an awareness for such a feasible technique. However a larger sample size would be required to carry out its evaluation as an alternative to IIF and as a screening technique.

Adult↗

PubMed1997

[Breast lesions undergoing needle aspiration. Studies of the Senology Section of SIRM (the Lombard Group). L'Associazione Italiana di Radiologia Medica].

INTRODUCTION: The SIRM study group for senology in Lombardy (GRESS-Lombardy) promotes meetings about discipline-related subjects and continuing medical education; it also tests and compares different procedures and collects and analyzes the data relative to large series of patients. We considered the breast lesions submitted to FNAB as the first study subject. MATERIALS AND METHODS: Clinical, technical, radiologic and cyto-histologic data were collected using a form and the results analyzed statistically. In 7 months (January to July, 1996), 23,952 women underwent mammography: 1405 lesions were detected and submitted to FNAB which helped diagnose 373 malignant, 951 benign and 81 nonclassified lesions. FNAB is performed in all our centers since cytologic examination is considered necessary for all the lesions classified, after mammography, as suspect or benign in women over 30 years old. FNAB is also performed on the lesions considered malignant after mammography. When suspect micro-calcifications are found, FNAB for cytologic purposes is performed in 8/11 centers; surgical biopsy is strictly recommended in 3/11 centers. RESULTS: Our personal results are reported in the 10 tables of this paper. Cytologic examination was inadequate in 11.8% of cases, negative in 58,4% and questionable in 5.2% of lesions, while malignancy was suspected in 7.2% of lesions. Cytologic findings were definitely malignant in 17.4% of lesions. CONCLUSIONS: The analysis of collected data can provide the operator with clear guidelines for common diagnostic protocols. All series of cases must obviously be recorded and analyzed to promote self-evaluation and comparison criteria, which are the basics to improve the accuracy of the radiologists devoted to senology.

Biopsy, Needle↗

PubMed2004

Maternal and congenital syphilis programmes: case studies in Bolivia, Kenya and South Africa.

Preventing congenital syphilis is not technically difficult, however operational difficulties limit the effectiveness of programmes in many settings. This paper reports on programmes in Bolivia, Kenya, and South Africa. All three countries have established antenatal syphilis control programmes. Early antenatal syphilis screening and management of positive cases were difficult to implement since most women presented for their first antenatal clinic visit after 6 months of pregnancy. Most women had rapid plasma reagin (RPR) testing; results were available on the same day in some clinics but took up to 4 weeks in others. No clinic had a system for tracking RPR-reactive women who did not return for their results. There were no guidelines for providers in Kenya and Bolivia. In all countries, supplies, drugs, notification cards, and other consumables were often unavailable. Health-care providers were unmotivated in Kenya and reported an excessive client load. In South Africa and Kenya some clients reported at their exit interview that they had never heard of syphilis nor had they been informed why blood was collected. Several prevention strategies could be implemented at the clinic level. These include encouraging women to attend for antenatal care before the fourth month of pregnancy, providing point-of-care testing so that results are available immediately and women who test positive can be treated, implementing presumptive treatment of sexual partners of women who test positive, adding a second test later in pregnancy so that incident cases can be managed, and improving the quality of syphilis care during pregnancy, delivery, and the neonatal period.

Bolivia↗

PubMed1990

Epidemiology of human papilloma virus infections and genital neoplasia.

The reliable assessment of epidemiology of genital HPV infections is hampered by a number of technical problems. Until recently, methods based on morphological approaches played a central role in HPV diagnosis, i.e. macromorphology, colposcopy, cytology and histopathology, supplemented by immunohistochemical and DNA-hybridization techniques and most lately by DNA amplification with PCR. Because of the fact that these morphological techniques are extremely difficult to standardize, they are subject to major variations, both interobserver and intraobserver. Further confusion in the field is created by the biological behaviour of HPV infections. As established by the long-term prospective follow-up study run in Kuopio since 1981 and including over 500 women, clinical progression and regression were significantly related to grade of the lesion at the time of diagnosis (p less than 0.00001, and p = 0.0005, respectively), as well as to the type of HPV (p = 0.0012). Most importantly, however, genital HPV infections seem to run an extremely fluctuating course, a passage from a manifest to a subclinical or latent infection being frequently encountered in individual patients when examined at 6-month intervals for prolonged periods. This explains the significantly divergent prevalence figures reported in different series (ranging from 2% to 80%), which are completely dependent on the technique used to analyse the presence of HPV, i.e., whether (a) PAP smear, (b) biopsy, (c) DNA hybridization, or (d) PCR amplification. The first two are capable of disclosing only manifest (clinical) infections, the latter two also (at least theoretically) the subclinical and latent ones. In unselected Finnish female population at the age of 22 years, the prevalence of clinical (i.e. detectable by PAP smear) HPV infections was about 3%, and the adjusted annual incidence was 8.0%. According to the estimates for the life-time risk, up to 79% of the Finnish females would contract at least one HPV infection within ages 20 to 79 years. When related to the long-term trends in invasive cervical cancer in Finland (data available between 1953-1988), the figures indicate that this 79% life-time risk of getting HPV-infected or even the observed 15% of clinical progression rate for HPV infections in the prospective follow-up study by no means signify an identical risk for development of cervical cancer (i.e. 0.79 X 0.15 = 11%). It seems likely that in countries where mass-screening programmes exist (and precancer lesions are traced and eradicated), the high prevalence of HPV infections is not necessarily reflected as increased prevalence figures of invasive cervical carcinomas.(ABSTRACT TRUNCATED AT 400 WORDS)

Carcinoma, Squamous Cell↗

PubMed1976

Measurement of carbon dioxide in blood.

The remarkable combination of physical and chemical properties displayed by carbon dioxide has enabled the development of a very wide variety of analytical methods for its measurement in blood or blood plasma. Both for historical and technical reasons, the gasometric method of Van Slyke and Neill is preeminent, but great skill is needed to realize its full precision and accuracy. The microgasometer of Natelson, however, has served the clinical laboratory well as a practicable manual means of microanalysis for total carbon dioxide. So far as automated analysis is concerned, it is highly significant that one of the first applications of Skegg's continuous flow principle was to the titrimetric determination of total carbon dioxide in serum; the AutoAnalyzer technique remains the most widely used of its kind, in spite of inherent difficulties in specimen handling, instrumental standardization, and quality control. At the same time, it has been pointed out that the routine determination of total carbon dioxide in serum does not offer a useful screening procedure for identifying or characterizing patients with acid-base disorders; full assessment of acid-base status, including pCO2 in selected patients is much more rewarding. The credit for bringing pCO2 measurements within the scope of the clinical laboratory, by means of the interpolation technique, is largely due to Astrup and his colleagues. Nevertheless, continual improvements have been made in the design and performance of the Severinghaus type of pCO2 electrode, so that reliable instruments offering direct readout of blood pCO2 are available from several manufacturers. The more elaborate versions of these instruments are rugged and work-simplified, and they offer automated self-calibration and end-point detection for pH and pO2, as well as pCO2. It will be surprising if such instruments do not come into widespread use.

Animals↗

PubMed2005

[Contributions of the epidemiological cancer registries to the evaluation of mammography screening in Germany].

INTRODUCTION: Before the country-wide introduction of mammography screening, testing of the organised screening took place in Weser-Ems, Bremen and Wiesbaden. Important quality assurance parameters (carcinomas detected during checkup intervals, tumour stage distribution, breast cancer incidence rate, breast cancer mortality rate) are to be evaluated via epidemiological cancer registries. For the model region Weser-Ems (MSWE) the record linkage with the epidemiological cancer registry Lower Saxony (EKN) was successfully accomplished. The technical realisation and first comparison analyses for the development of breast cancer incidence and of tumour size are reported. MATERIAL AND METHODS: The target population of the MSWE was 22,600 women aged 50-69 years. They were invited since May 2002 to mammography screening with a screening interval of two years. The record linkage of 12,913 women who participated until February 2004 in the MSWE, was realised by the use of the control number system of the epidemiological cancer registries. The observation time was between 6 and 25 month (median: 15 month). Reference population for comparison analyses were all women between 50 and 69 years of the remaining governmental district Weser-Ems (255,000 women). RESULTS: In the first record linkage 96 screening-cases (ICD-10 C50 + D05) could be identified. Additionally six interval cancers were determined (time between screening and diagnosis in months: median 5.5; mean 7.7). The breast cancer incidence increased in the MSWE area and in the control-area, the rise in the MSWE area being higher. The increase was especially observed with the small tumours. Women with breast cancer diagnosed by screening: 19.8% in-situ-cancer and 18.8% very small tumours < = 10 mm. In the control area Weser-Ems this rate with 5.6% in-situ-cancer and 14.5% very small tumours, was relatively high, indicating the spread of opportunistic mammographies in absence of organised screening. CONCLUSION: First effects of mammography screening can be evaluated early by comparison between screening data and the data of population-based cancer registries. Using the control number system of the epidemiological cancer registries and comparison by pseudonyms the evaluation of quality assurance parameters of the MSWE can be realised in compliance with the data security law. The feedback of cancers, detected during checkup intervals is not covered by the cancer registry law. For the implementation of the guidelines for early recognition cancer legal adjustments will be necessary. This concept can be easily adapted to other screening programme.

Age Factors↗

PubMed2006

A test of performance of breast MRI interpretation in a multicentre screening study.

OBJECTIVES: The aim of this study was to assess the consistency and performance of radiologists interpreting breast magnetic resonance imaging (MRI) examinations. MATERIALS AND METHODS: Two test sets of eight cases comprising cancers, benign disease, technical problems and parenchymal enhancement were prepared from two manufacturers' equipment (X and Y) and reported by 15 radiologists using the recording form and scoring system of the UK MRI breast screening study [(MAgnetic Resonance Imaging in Breast Screening (MARIBS)]. Variations in assessments of morphology, kinetic scores and diagnosis were measured by assessing intraobserver and interobserver variability and agreement. The sensitivity and specificity of reporting performances was determined using receiver operating characteristic (ROC) curve analysis. RESULTS: Intraobserver variation was seen in 13 (27.7%) of 47 of the radiologists' conclusions (four technical and seven pathological differences). Substantial interobserver variation was observed in the scores recorded for morphology, pattern of enhancement, quantification of enhancement and washout pattern. The overall sensitivity of breast MRI was high [88.6%, 95% confidence interval (CI) 77.4-94.7%], combined with a specificity of 69.2% (95% CI 60.5-76.7%). The sensitivities were similar for the two test sets (P=.3), but the specificity was significantly higher for the Manufacturer X dataset (P<.001). ROC curve analysis gave an area under the curve of 0.85 (95% CI 0.79-0.92) CONCLUSIONS: Substantial variation in all elements of the scoring system and in the overall diagnostic conclusions was observed between radiologists participating in MARIBS. High overall sensitivity was achieved with moderate specificity. Manufacturer-related differences in specificities possibly occurred because the numerical thresholds set for the scoring system were not optimised for both equipment manufacturers. Scoring systems developed on one equipment software may not be transferable to other manufacturers.

Breast Neoplasms↗

PubMed1993

Screening and prenatal diagnosis of the haemoglobinopathies.

In this paper we have reviewed the social and technical aspects of carrier screening and prenatal diagnosis of the inherited haemoglobinopathies. The characteristics of programmes based on carrier screening and prenatal diagnosis ongoing in a number of at-risk Mediterranean populations have been described. The most relevant and common aspects of these programmes are the continuous educational campaign directed to the population at large, the voluntary basis and non-directive counselling. The target population has been most commonly couples before or after marriage. The vast majority of couples counselled accepted prenatal diagnosis. All programmes have encountered a high degree of success as indicated by the marked reduction in the birth rate of infants with thalassaemia major. No significant adverse effects have been reported. A programme with similar characteristics and for which the preliminary results are encouraging, is operating for sickle cell anaemia in the Cuban population. In a population with high frequency of hydrops fetalis, screening for deletion alpha-thalassaemia is recommended to prevent the negative effects on a pregnant woman of the presence of an hydropic fetus. Thalassaemia carrier screening is now carried out by automatic red cell indices and HbA2 determination. Definition of atypical cases may require iron studies, globin chain synthesis determination and/or alpha, beta- and delta-globin gene analysis. Identification of the carrier state is followed by definition of the mutation on enzymatically amplified DNA. Known mutations may be detected by restriction endonuclease analysis, non-denaturing polyacrylamide gel electrophoresis, allele-specific primers or allele-specific probes. The most promising procedures, which are also amenable to complete automation are reverse oligonucleotide hybridization and primer-specific amplification. Unknown mutations are defined by denaturing gradient gel electrophoresis, single-strand conformation polymorphism analysis, and chemical mismatch cleavage analysis followed by direct sequencing. The same methods on enzymatically amplified chorionic villus DNA are used for prenatal diagnosis. The potential pitfall resulting from maternal contamination can be avoided by careful dissection of the maternal decidua from the chorion and by the simultaneous amplification of a suitable polymorphism.

DNA Restriction Enzymes↗

PubMed1993

Status of tuberculosis control in Thailand.

The national tuberculosis control program (NTP) was implemented in Thailand as integrated with the provincial general health services since 1967, with BCG vaccination successfully introduced from the beginning, but progress in expansion of case-finding and chemotherapy had only been achieved following the establishment of hospitals at the district level since the late seventies. At present, case-detection and treatment have operated in more than 95% of the 600 district hospitals and 87 hospitals at provincial and regional levels, with patient follow-up by health centers, logistically supported and technically supervised by 12 zonal TB centers. The trend of the disease has shown noticeable decline as indicated by the three national surveys in 1962, 1977 and 1991, that is, morbidity rate as suspected by x-ray of 2.1%, 1.4% and 1.01%; infectious case rate of 0.5%, 0.31% and 0.24% respectively, a reduction of about 2-3% per year. The infection rate of children 0-14 years of age was found to be 15.2% in 1977; 8.9% in 1983; and 5.18% in 1987, giving the annual risk of infection (ARI) of 4.9%, 2.3% and 2.0% respectively. Currently the program detects and treats about 31,000 smear-positive TB cases plus an equal number of smear-negative cases per year. Short-course chemotherapy was introduced since 1985 and expanded to cover all the former by 1991, resulting in improvement of the treatment success rate from less than 50% when using the old standard 18-24 months regimen to 70-80%. As the coverage of case detection and treatment is still only about 60% of the incidence or 30% of the prevalence, trials of primary health care approach have yielded substantially increased case detection coverage as well as improved cure rates. BCG vaccination as part of the Expanded Program on Immunization has reached 90-100% coverage of infants.

Adolescent↗

PubMed2005

The problems with risk selection; scientific and psychosocial aspects.

Between 9,000 and 18,000 new cases of breast cancer per year in the United States are associated with a genetically defined predisposition. Mutations in BRCA1 and 2 account for greater than 60% of inherited breast cancer. Mutations in additional undiscovered high and low penetrance genes may account for the other 40% of inherited breast cancer cases and possibly a subset of familial breast cancer cases that lacks an autosomal-dominant pattern of inheritance. False-negative rates resulting from gene sequencing of BRCA1 and 2 may be as high as 10%-15%, making the identification of high-risk individuals a complex and often futile process for both patient and physician. As a consequence of technical limitations in BRCA1 and 2, genetic testing and the lack of comprehensive breast cancer prediction models that take into account both genetic and environmental factors, we are unable to quantify future breast cancer risk for many patients. This uncertainty often leads to the exclusion of high-risk individuals in screening and prevention trials, which is perhaps most evident in breast cancer screening trials incorporating the use of magnetic resonance imaging (MRI) to identify early cancers. These studies demonstrate that MRI increases the sensitivity of a screening protocol in mutation carriers and succeeds at detecting earlier stage cancers. Eligibility criterion for most of these trials was documented mutations in BRCA1 and 2 or future breast cancer risk predicted by family history or models, thereby possibly excluding women at significantly elevated risk that testing failed to identify or whose risk is not adequately reflected based on current models used in risk assessment. We may be turning very high-risk women away from screening trials, recommending yearly mammography and clinical breast exam, when neither will be adequate for detecting their cancers early. In addition, the impact of risk-reducing strategies including bilateral prophylactic oophorectomy (BSO) and tamoxifen has not been analyzed in these studies. For example, a 40-year-old BRCA2 carrier may only have a 10% and 50% lifetime risk of ovarian and breast cancer, respectively, and interventions including tamoxifen and breast MRI screening may significantly reduce the risk of both getting breast cancer and dying from it, thereby obviating the need for early screening or prophylactic surgeries, permitting these women to defer the quality of life struggles until they are older. A larger sample size is needed to determine the degree to which different subgroups of high-risk patients will benefit from MRI screening, with particular attention to women who have undergone BSO or who are taking tamoxifen. The challenges in risk selection are numerous and produce more questions than answers with regard to screening and management of high-risk individuals. In the future, we hope that early detection tools, risk-reduction strategies, and risk assessment preclude the need for prophylactic surgeries, inappropriate selection of patients for screening, and the associated decisions that compromise our patients' quality of life.

Breast Neoplasms↗

PubMedDate not supplied

Application of a simplified comparative genomic hybridization technique to screen for gene amplification in pediatric solid tumors.

Conventional cytogenetic analysis of solid tumors is technically very demanding and requires a large number of viable cells. The technique of comparative genomic hybridization (CGH) circumvents these difficulties and has been shown to be particularly useful for identifying new gene amplifications. We have simplified the CGH technique for the detection of amplifications by utilizing a single labeling approach in which labeled tumor DNA is mixed with unlabeled normal human DNA and hybridized to normal metaphases on a slide. To examine the consistency and sensitivity of the method, initial experiments were performed using a retinoblastoma (RB) cell line and five pediatric solid tumors known to contain an amplification. The technique was easy to use and sensitive enough to detect low-level amplifications. The RB cell line showed reproducible signals at 2p24, indicative of amplified sequences, on both homologues in 95% of the metaphases (> 30) examined. Amplifications of the MYCN gene (2p24) were detected in three alveolar rhabdomyosarcomas and one medulloblastoma. CGH was then applied to six tumors in a prospective fashion, before data about specific gene amplification were available. In two, amplification of the MDM2 gene (12q13-14) was identified using CGH and later confirmed by Southern blot analysis. Four tumors negative for MDM2 and MYCN amplifications by CGH analysis were also negative by Southern blot analysis. Gene amplification as low as fourfold was detected in one tumor and the overall pattern of gene amplification detected by CGH in these tumors was not complex, involving just one amplification site for each case. Therefore, this simplified CGH technique is suitable for routine screening of pediatric solid tumors for amplifications when genetic studies are important but sample sizes are small and dividing cells are infrequent or unavailable.

Blotting, Southern↗

PubMed2002

Benefits and drawbacks of including consumer reviewers in the scientific merit review of breast cancer research.

BACKGROUND: This study assessed participant opinions about inclusion of breast cancer survivors as lay representatives in a scientific and technical merit review of proposals for the 1995 Department of Defense Breast Cancer Research Program (DOD BCRP). METHODS: The evaluation employed a prepanel and postpanel survey design, which was intended to elicit feedback about attitudes, perceptions, and beliefs toward collaborative consumer and scientist participation in scientific merit review. Qualitative methods were used to describe the consumers' and scientists' responses, to explore the significance of this interaction, and to gain an understanding of the benefits and disadvantages of bringing these participants together. RESULTS: Both groups were initially troubled about the consumers' lack of scientific background and questioned their qualifications and preparation for participation in a scientific panel. In particular, consumers were concerned that their judgments would not be taken seriously by scientists, a concern somewhat lessened by participation. After the meeting, scientists viewed the consumers as hard-working, dedicated survivors and advocates and endorsed the presence of carefully chosen lay panel members. Scientists were troubled that consumers potentially would have an impact on voting and on the subsequent scoring of proposals, a concern that was not validated by quantitative findings. CONCLUSIONS: As a result of these data, the DOD BCRP continues to embrace clarify the nature of collaborative participation in scientific merit review.

Adult↗

PubMed2005

A survey of the methods for the characterization of microbial consortia and communities.

A survey of the available literature on methods most frequently used for the identification and characterization of microbial strains, communities, or consortia is presented. The advantages and disadvantages of the various methodologies were examined from several perspectives including technical, economic (time and cost), and regulatory. The methods fall into 3 broad categories: molecular biological, biochemical, and microbiological. Molecular biological methods comprise a broad range of techniques that are based on the analysis and differentiation of microbial DNA. This class of methods possesses several distinct advantages. Unlike most other commonly used methods, which require the production of secondary materials via the manipulation of microbial growth, molecular biological methods recover and test their source materials (DNA) directly from the microbial cells themselves, without the requirement for culturing. This eliminates both the time required for growth and the biases associated with cultured growth, which is unavoidably and artificially selective. The recovered nucleic acid can be cloned and sequenced directly or subpopulations can be specifically amplified using polymerase chain reaction (PCR), and subsequently cloned and sequenced. PCR technology, used extensively in forensic science, provides researchers with the unique ability to detect nucleic acids (DNA and RNA) in minute amounts, by amplifying a single target molecule by more than a million-fold. Molecular methods are highly sensitive and allow for a high degree of specificity, which, coupled with the ability to separate similar but distinct DNA molecules, means that a great deal of information can be gleaned from even very complex microbial communities. Biochemical methods are composed of a more varied set of methodologies. These techniques share a reliance on gas chromatography and mass spectrometry to separate and precisely identify a range of biomolecules, or else investigate biochemical properties of key cellular biomolecules. Like the molecular biological methods, some biochemical methods such as lipid analyses are also independent of cultured growth. However, many of these techniques are only capable of producing a profile that is characteristic of the microbial community as a whole, providing no information about individual members of the community. A subset of these methodologies are used to derive taxonomic information from a community sample; these rely on the identification of key subspecies of biomolecules that differ slightly but characteristically between species, genera, and higher biological groupings. However, when the consortium is already growing in chemically defined media (as is often the case with commercial products), the rapidity and relatively low costs of these procedures can mitigate concerns related to culturing biases. Microbiological methods are the most varied and the least useful for characterizing microbial consortia. These methods rely on traditional tools (cell counting, selective growth, and microscopic examination) to provide more general characteristics of the community as a whole, or else to narrow down and identify only a small subset of the members of that community. As with many of the biochemical methods, some of the microbiological methods can fairly rapidly and inexpensively create a community profile, which can be used to compare 2 or more entire consortia. However, for taxonomic identification of individual members, microbiological methods are useful only to screen for the presence of a few key predetermined species, whose preferred growth conditions and morphological characteristics are well defined and reproducible.

Bacteria↗

PubMed1995

Comparison of HLA-DRB1 typing by DNA-RFLP, PCR-SSO and PCR-SSP methods and their application in providing matched unrelated donors for bone marrow transplantation.

The aim of the study was to devise a strategy for large batch analysis to determine HLA Class II alleles exhibited by candidate bone marrow transplant donors and prospective recipients using previously published DNA-based typing techniques. Special attention was directed towards the technical aspects of procedures, the level of typing resolution and the speed of data analysis. 200 blood samples from volunteer bone marrow transplant donors typed serologically for HLA-DR and DQ were further investigated using three DNA-based typing methods: (i) restriction fragment length polymorphism (RFLP) analysis, (ii) polymerase chain reaction (PCR) amplification and subsequent hybridisation with sequence specific oligonucleotide probes (PCR-SSO), and (iii) PCR amplification with sequence specific primers (PCR-SSP) to resolve the DRB1* specificity of each individual. In general, the HLA-DR results obtained using PCR-SSO and PCR-SSP correlated well with each other. However, discordant results were obtained between PCR and RFLP based typing in 21 cases, especially in relation to DRB3* alleles associated with the DRB1 gene. These differences were due to three problems pertaining to RFLP analysis: i) alleles with identical DRB, DQA and DQB fragment sizes, ii) reliance on DQA and DQB results to assign the DRB genotype, and iii) a "new polymorphism" of DR7, in a DR7 homozygous, exhibiting a fragment similar in size to DR8. Our findings suggested a strategy requiring PCR-SSO analysis for initial low resolution class II typing involving large numbers of samples, while the use of PCR-SSP is reserved for small numbers of samples, for urgent samples or for situations where higher resolution is required.(ABSTRACT TRUNCATED AT 250 WORDS)

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