Chronic myelogenous leukemia--progress at the M. D. Anderson Cancer Center over the past two decades and future directions: first Emil J Freireich Award Lecture.
The purpose of this study was to review the progress in clinical and translational research in chronic myelogenous leukemia (CML) over the past 20 years at M.D. Anderson Cancer Center. The CML database updating the clinical and basic research investigations was reviewed as the source of this report. Publications resulting from these investigations were summarized. The long-term results with intensive chemotherapy, IFN-alpha therapy alone or in combination, autologous stem cell transplantation, and new agents such as homoharringtonine and decitabine showed encouraging results. Biological studies related to the BCR-ABL molecular abnormality, other molecular events, and the detection of minimal residual disease were detailed. Future strategies with potential promise in CML were outlined. Significant progress in understanding CML biology and in treating patients afflicted with the disease has occurred. Several therapeutic and research tools are currently investigated, which should hopefully improve further the prognosis of patients with CML. (+info)
The hypoxic cell: a target for selective cancer therapy--eighteenth Bruce F. Cain Memorial Award lecture.
It has been appreciated for more than 50 years that very low levels of oxygenation, or hypoxia, both protect cells from killing by X-irradiation and are present in solid tumors but not in normal tissues. Until recently, however, there has been no definitive proof that hypoxia in human tumors contributes to radiotherapy treatment failure. We now know that hypoxia in solid tumors is not only a major problem for radiation therapy but also leads to resistance to most anticancer drugs and, importantly, appears to accelerate malignant progression and increase metastasis. To date, efforts to overcome the problem of hypoxia have had only limited success. However, the recent development of new drugs that are nontoxic until they are activated in the hypoxic cell opens a new era. The first of these new drugs to be tested clinically, tirapazamine, a drug that is highly toxic to hypoxic but not aerobic cells, has already demonstrated efficacy in selective potentiation of cisplatin in randomized Phase III trials with non-small cell lung cancer. The unique presence of hypoxic cells in human tumors provides an important target for selective cancer therapy. (+info)
A profile of the members of FASEB societies: NIH awards, degrees, and institutional affiliations, 1999.
Data from the FASEB Directory of Members and NIH were used to develop a statistical profile of the members of FASEB Societies. For the U.S.-based scientists (exclusive of retired and student members), the most frequently reported degree was a research doctorate (69. 6%). A substantial fraction, however, reported medical degrees (19. 2%) or both research and medical degrees (8.0%). The majority of members of FASEB Societies listed academic affiliations in the directory. Industrial affiliations were reported, however, in 9.7% of the entries with smaller fractions listing associations with hospitals, independent research institutes, and government agencies. Just over one-fourth of the members of FASEB Societies were principal investigators on NIH research grants. These investigators received one-half of all NIH grants and nearly 60% of the RO1 grants. (+info)
Remembrance of things past and concerns for the future.
Stanley G. Schultz received the seventh annual Arthur C. Guyton Physiology Teacher of the Year Award. The following is a speech he delivered as he was presented the award at Experimental Biology '99 in Washington, DC, in April 1999. (+info)
The development of the index of complexity, outcome and need (ICON).
This paper is based on the winning submission for the 1998 Chapman prize awarded by the British Orthodontic Society for an essay on a subject promoting the interests of orthodontics. The aim of the investigation is to develop a single index for assessing treatment inputs and outcomes. An international panel of 97 orthodontists gave subjective judgements on the need for treatment, treatment complexity, treatment improvement, and acceptability on a diverse sample of 240 initial and 98 treated study models. The occlusal traits in the study models were scored according to a defined numerical protocol. Five highly predictive occlusal traits were identified (IOTN Aesthetic Component, crossbite, upper arch crowding/ spacing, buccal segment antero-posterior relationships, and anterior vertical relationship) and then used to 'predict' the panelist's decisions using regression analysis. Cut-off values were determined for the dichotomous judgements by plotting specificity sensitivity and overall accuracy. Twenty percentile ranges were used to determine 5 grades of complexity and improvement. The index prediction of decisions for treatment need, had specificity 84.4 per cent, sensitivity 85.2 per cent, and overall accuracy 85 per cent. When used to predict treatment outcomes, the new index had specificity 64.8 per cent, sensitivity 70.1 per cent, and overall accuracy 68.1 per cent. The index could explain 75.6 per cent of the variance in the mean casewise complexity score and 63.5 per cent of the mean casewise improvement score. A new orthodontic index is proposed to assess treatment need, complexity, and outcome. It is based on international orthodontic opinion. (+info)
Theodore Woodward Award. Pathogenesis of biochemical abnormalities in protoporphyria.
In summary, FC gene mutations in patients with protoporphyric liver disease typically cause major structural alterations in the FC protein. However, the gene mutations by themselves do not satisfactorily account for the severe phenotype, as the same mutations are found in asymptomatic family members, and similar mutations are found in patients who do not develop liver disease. Thus there may be unidentified factors in the FC gene locus, or factors outside the locus, which are also important in determining the degree of protoporphyrin accumulation that occurs in an individual patient, hence, the potential for developing significant liver disease. Further studies are needed to clarify this possibility and identify those factors. (+info)
The EFQM excellence model: European and Dutch experiences with the EFQM approach in health care. European Foundation for Quality Management.
One way to meet the challenges in creating a high performance organization in health care is the approach of the European Foundation for Quality Management (EFQM). The Foundation is in the tradition of the American Malcolm Baldrige Award and was initiated by the European Commission and 14 European multi-national organizations in 1988. The essence of the approach is the EFQM Model, which can be used as a self-assessment instrument on all levels of a health care organization and as an auditing instrument for the Quality Award. In 1999 the EFQM Model was revised but its principles remained the same. In The Netherlands many health care organizations apply the EFQM Model. In addition to improvement projects, peer review of professional practices, accreditation and certification, the EFQM Approach is used mainly as a framework for quality management and as a conceptualization for organizational excellence. The Dutch National Institute for Quality, the Instituut Nederlandse Kwaliteit, delivers training and supports self-assessment and runs the Dutch quality award programme. Two specific guidelines for health care organizations, 'Positioning and Improving' and 'Self-Assessment', have been developed and are used frequently. To illustrate the EFQM approach in The Netherlands, the improvement project of the Jellinek Centre is described. The Jellinek Centre conducted internal and external assessments and received in 1996, as the first health care organization, the Dutch Quality Prize. (+info)
Lynch syndrome: genetics, natural history, genetic counseling, and prevention.
Lynch syndrome is the most common hereditary form of colorectal cancer (CRC). Its natural history has been investigated extensively, so that highly targeted surveillance and management strategies, melded to its natural history, have proven effective in cancer control. Most important is the early age of onset of cancer (approximately 44 years), involving CRC and the several extracolonic cancers that are integral to the syndrome. With respect to CRC, approximately 70% of cases occur proximal to the splenic flexure. Synchronous and metachronous CRCs are extremely common. Full colonoscopy should be initiated when the patient is between the ages of 20 and 25, and because of the accelerated carcinogenesis of CRC, it should be performed every 1 to 2 years. The presence of initial CRC requires subtotal colectomy, given the mentioned increased frequency of metachronous cancer. Options available for germ-line mutation carriers, in addition to cancer screening, include prophylactic colectomy as well as prophylactic total abdominal hysterectomy and bilateral salpingo-oophorectomy. The discovery of mismatch repair germ-line mutations (most commonly MSH2 or MLH1) has added significantly to the recognition of this disease as well as to the search for high-risk individuals throughout families who, with genetic counseling, may become candidates for germ-line mutation testing. Clearly, hereditary nonpolyposis colorectal cancer provides an excellent opportunity for learning about the etio-pathogenesis of cancer at the molecular and clinical levels and how this knowledge might ultimately be exploited for cancer control. A search for chemoprevention agents, such as cyclo-oxygenase 2 inhibitors, as well as for putative environmental effects and how they may interact with the genetic component in CRC etiology should abet this entire cancer control process. (+info)