Linguistic theory and operant procedures: toward an integrated approach to language training for the mentally retarded.
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Biomedical subjects
Publications and source records attributed to J Lynch.
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The repair of medial orbital blow-out fractures remains a challenging surgical procedure for most surgeons. Endoscopic intranasal visualization of the medial orbital wall or lamina papyracea is a technique familiar to most otolaryngologists. This endoscopic view would allow for confirmation of orbital content reduction and bimanual manipulation of an orbital implant. To determine the effectiveness of a new surgical technique, a cadaveric study was performed to evaluate the ability to (1) reduce the herniated orbital contents and (2) restore the normal anatomic orbital configuration and volume with the addition of an orbital implant. Excellent visualization of the fracture was achieved in all cadaveric specimens. In addition, endoscopic intranasal visualization of the medial orbital wall greatly facilitated the anatomic reduction of orbital contents and proper placement of the orbital implant. The surgical technique is described and a clinical case is reported in which this endoscopic technique was effectively used. Arch Facial Plast Surg. 2000;2:269-273
Hereditary breast cancer (HBC) shows extant clinical and genetic heterogeneity. Clinically one finds the onset of breast cancer at an early age, an excess of bilaterality, and patterns of multiple primary cancer such as combinations of breast and ovarian carcinoma in the hereditary breast-ovarian cancer (HBOC) syndrome. In addition to HBOC, one sees a variety of putative breast cancer-prone genotypes inclusive of hereditary site-specific breast cancer, and the Li-Fraumeni (SBLA) syndrome that is characterized by cancers involving all three germinal layers including sarcomas, brain tumors, leukemia, lymphoma, and adrenal cortical carcinoma in addition to often markedly early-onset breast cancer. Breast cancer is also associated with autosomal dominantly inherited Cowden's disease and autosomal recessively inherited ataxia-telangiectasia. Examples of pedigrees depicting clinical examples of these several HBC syndromes are presented in order to describe HBC's heterogeneity. The recent identification of the BRCA1 gene in early-onset hereditary site-specific breast cancer and the HBOC syndrome has led to new challenges for the genetic counselor. We review genetic counseling, which embraces surveillance and management recommendations that are responsive to the natural history of HBC and address the concept for future development of centers of expertise for HBC in the interest of improving cancer control.
The present experiments were designed to evaluate in vivo the differential sensitivity of tumor cell subpopulations to hormone and polyamine manipulations using the hormone-responsive N-nitrosomethyl-urea (NMU)-induced rat mammary tumor. NMU tumor bearing rats were randomly assigned to control, ovariectomy, alpha-difluoromethyl-ornithine (DFMO) administration (an inhibitor of polyamine biosynthesis), or combination treatment, and were sacrificed on day 2, 4, or 7. The proportion of different cells was estimated by morphometric analysis and their replicative activities by [3H]-thymidine autoradiography. In tumors of intact rats, the fractions of glandular, myoepithelial, and non-epithelial cells were 85.3 +/- 2.2%, 4.7 +/- 0.7%, and 9.9 +/- 1.9%, respectively. Ovariectomy induced a similar time-dependent decline in the labelling indices of each cell type (from 5% to 1%). It also decreased the fraction of glandular cells (74.9 +/- 4.5%), while increasing the fraction of myoepithelial (8.6 +/- 1.9%) and non-epithelial (16.3 +/- 3.2%) cells. DFMO exerted similar but more modest effects. DFMO-induced tumor regression was also inferior to that observed with ovariectomy. Combined ovariectomy and DFMO induced a faster and greater suppression of all labelling indices than the individual treatments, even though tumor regression was not superior to that produced by ovariectomy alone. Combination treatment also produced more profound morphologic changes, reducing the fraction of glandular cells to 64.4 +/- 3.9% and increasing that of non-epithelial cells to 26.6 +/- 4.4%. Ovariectomy and DFMO reduced height but not width of glandular cells, resulting in a modest decrease in cell volume. The combination treatment, however, significantly suppressed all three parameters.(ABSTRACT TRUNCATED AT 250 WORDS)
The present experiments were designed to evaluate the polyamine involvement in hormonal actions on proliferation and receptor content of neoplastic tissue (hormone-responsive breast cancer) as well as on growth of normal endocrine target tissue (uterus) in the same animals. Administration of estradiol and perphenazine (to stimulate endogenous prolactin release) stimulated N-nitrosomethyl-urea (NMU)-induced rat mammary tumor growth following ovariectomy-induced tumor regression. Such hormonal activation of breast cancer growth was completely abolished by treatment with alpha-difluoromethyl-ornithine (DFMO), a specific irreversible inhibitor of ornithine decarboxylase, which lowered tumor content of polyamines. The growth inhibitory effect of DFMO was partially reversible by exogenous putrescine administration. In contrast, the rise in cytosolic content of progesterone receptors induced by hormonal treatment was not affected by suppression of tumor polyamine levels by DFMO. Similarly, DFMO administration failed to influence the hormone-induced increase in uterine weight in the same animals. Thus, our data suggest selectivity of polyamine involvement in hormone actions, which, in our experimental system, seems to be restricted to the endocrine control of neoplastic cell proliferation.
BACKGROUND: Little is known regarding patients' views and levels of satisfaction with out-of-hours care in Irish general practice despite significant recent changes in service delivery. AIMS: This study aimed to record patients' experience of out-of-hours care on a specific occasion and elicit their satisfaction with out-of-hours care in general. METHODS: Patients requesting out-of-hours care in three south inner city Dublin practices in June and July 2000 were identified and sent an anonymous postal questionnaire. RESULTS: Two hundred and forty patients were identified and 58% responded to the questionnaire. The approximate call rate was 195 calls per 1,000 patients per year. Sixty-one per cent of patients used the co-operative service, 28% received a house call and 3% received telephone advice only; 86% are currently satisfied with out-of-hours care. CONCLUSIONS: The majority of patients are satisfied with the current out-of-hours service. Telephone consultation rates are significantly lower than other countries. These findings need to be considered before the widespread introduction of systems involving increased telephone consultations.
Hereditary non-polyposis colorectal cancer (HNPCC) is the most common hereditary form of colorectal cancer (CRC), accounting for approximately 10% of the total CRC burden. HNPCC lacks premonitory physical stigmata, thereby making the family history crucial for diagnosis. Advances in molecular genetics during the past 2 years have led to the cloning of four HNPCC genes (MHS2, MLH1, PMS1 and PMS2). It is now possible to provide presymptomatic DNA testing followed by genetic counselling for gene carriers. Some studies have shown that adenomas in HNPCC are larger, more villous, and have more high grade dysplasia than sporadic cases, suggesting an accelerated adenoma-carcinoma sequence. Given the early age of onset and proximal predominance of CRC, we initiate colonoscopy at age 20-25 years and we recommend that it be performed every 1-2 years. The wealth of clinical and molecular genetic knowledge currently available to physicians about HNPCC can be used effectively for cancer control.
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The extracolonic tumor spectrum of hereditary nonpolyposis colorectal cancer (HNPCC) includes cancer of the endometrium, ovaries, stomach, biliary tract, and urinary tract. This study was designed to determine the penetrance of colorectal and extracolonic tumors in HNPCC mutation carriers. Forty-nine patients (22 females and 27 males) were identified with an MSH2 germline mutation, and 56 patients (28 females and 28 males) were identified with an MLH1 I mutation. Cumulative incidence by age 60 (lifetime risk) and mean age of cancer diagnosis were compared. The lifetime risk of extracolonic cancers in MSH2 and MLH1 carriers was 48% and 11%, respectively (P = 0.016). Extracolonic cancer risk in MSH2 females and males was 69% and 34%, respectively (P = 0.042). Mean age of extracolonic cancer diagnosis was significantly older for MSH2 males than females (55.4 vs. 39.0, P = 0.013). No difference was observed in colorectal cancer risk between MLH1 and MSH2 carriers (84% vs. 71%). Colorectal cancer risk was 96% in MSH2 males compared to 39% in MSH2 females (P = 0.034). No differences in colorectal and extracolonic cancer risks between MLH1 females and males were identified. The risk of extracolonic cancer by age 60 was greater in MSH2 mutation carriers than in MLH1 carriers. Gender differences in colorectal and extracolonic cancer risk were observed for MSH2 carriers only. These phenotypic features of HNPCC genotypes may have clinical significance in the design of genotype-specific screening, surveillance, and follow-up for affected individuals.
Four new fermenters were designed and constructed for use in secondary metabolite cultivations, bioconversions, and enzyme production. A new PC/PLC-based control system also was implemented using GE Fanuc PLCs, Genius I/O blocks, and Fix Dynamics SCADA software. These systems were incorporated into an industrial research fermentation pilot plant, designed and constructed in the early 1980s. Details of the design of these new fermenters and the new control system are described and compared with the existing installation for expected effectiveness. In addition, the reasoning behind selection of some of these features has been included. Key to the design was the goal of preserving similarity between the new and previously existing and successfully utilized fermenter hardware and software installations where feasible but implementing improvements where warranted and beneficial. Examples of enhancements include strategic use of Inconel as a material of construction to reduce corrosion, piping layout design for simplified hazardous energy isolation, on-line calculation and control of nutrient feed rates, and the use of field I/O modules located near the vessel to permit low-cost addition of new instrumentation.