Growth without risk? Build on your CCRC continuum with active adult housing.
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Biomedical subjects
Publications and source records attributed to J Moore.
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Trials of high dose immunosuppression and peripheral blood stem cell transplantation (PBSCT) in patients with severe rheumatoid arthritis (RA) have now commenced based on encouraging data from case reports of patients with coexistent malignancy and animal transplant models. Early case reports in Australia documented the potential for cure of RA in most patients receiving allogeneic or syngeneic transplants. However, the relatively high morbidity and mortality of these procedures has necessitated the use of autologous PBSCT. in accordance with international guidelines released by the EBMT/EULAR working party. Phase I trials in autologous PBSCT have seen substantial remissions of RA in the majority of patients who had previously failed all available therapies. Recurrence of disease occurs in most patients usually within 2 years; however, the use of disease modifying agents after recurrence results in substantial amelioration of the disease, again suggesting a form of "immunomodulation." This observation raises the possibility of maintenance therapy associated with procedure to prolong responses. Other modifications of the procedure are discussed, including T cell depletion of the graft, currently the subject of a randomized trial.
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OBJECTIVES: To provide optimum health care to indigenous people with diabetes, to prevent diabetes, and to monitor the epidemiology of diabetes and selected complications. The purposes of this paper are to describe the program and to present data that highlights the major problems and successes. STUDY DESIGN: Descriptive epidemiology report of diabetes and population service program based on yearly chart review data. METHODS: Almost half of Alaska Natives with diabetes have no direct access to physicians or hospitals. Health care delivery is now managed by the tribes themselves. Program emphases include maintenance of a population-based registry, formal training for village health aides, physical activity programs, patient education, primary prevention activities and adherence to standards of care to prevent complications. A centralized registry is maintained to assure that epidemiological data is available and patients are not lost to follow-up. Each year a random sample of charts at each major facility is audited against nationally standardized care guidelines. RESULTS: The prevalence of diabetes among Alaska Natives increased 80% over the 13 years from 1985 to 1998 (15.7/1000 to 28.3/1000, age adjusted to U.S. 1980 population). For the years 1986-1998 the incidence rates of lower extremity amputation and end stage renal disease were 6.1/1000 and 2.0/1000 respectively. The level of care provided to Alaska Native patients is comparable to that provided to the general diabetic patient population seen in Alaskan urban clinics. CONCLUSIONS: In spite of logistic challenges, care provided to Alaska Native people with diabetes compares favorably to that provided in other settings. Incidence rates of lower extremity amputation and end stage renal disease also remain comparable to or lower than those in other U.S. populations. Many aspects of our system could be extended to other chronic disease programs serving isolated indigenous populations. Primary prevention of diabetes remains a major challenge as life styles change.
Fibroblasts derived from the Rat2 parental cell line were genetically modified to express the cell-associated form of Sonic hedgehog (Shh) and then co-grafted along with E14 fetal ventral mesencephalon (VM) tissue into the denervated striatum of F344 rats; fetal VM grafts alone or co-grafts using the nonexpressing Rat2 fibroblasts served as controls. Seven weeks after grafting, co-grafts of fetal VM and fibroblasts expressing Shh (Rat2/Shh) contained significantly more tyrosine hydroxylase-positive (TH+) neurons than either the fetal VM grafts or co-grafts of fetal VM plus nonexpressing fibroblasts (Rat2). Despite a significantly higher yield of grafted TH+ neurons in the fetal VM + Rat2/Shh co-grafts than in either of the other two control groups, amphetamine-induced rotational behavior scores were not significantly different between any of the three treatment groups. The number of TH+ neurons in the Rat2 (nonexpressing) co-grafts was significantly lower than the other two treatment groups. The results from this study suggest that fibroblasts expressing Shh may improve the number of co-grafted dopamine neurons, but do not improve the functional capacity of the graft in terms of improving amphetamine-induced rotational behavior.
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Reverse transcriptase-PCR (RT-PCR) was carried out on total RNA prepared from the third-stage larvae (L3) of Ostertagia ostertagi in order to clone and characterize the major transcripts expressed in this larval stage, as an initial investigation of arrested larval development in the parasite. Distinct bands were visible on an agarose gel and four of these were cloned and sequenced. Three of the bands represented multiple transcripts, while the fourth band encoded the enzyme GTP cyclohydrolase I (GTP-CH), which catalyses the first and rate-limiting step in pteridine biosynthesis. Northern blot analysis and RT-PCR demonstrated that GTP-CH is highly up-regulated in the L3 stage and undetectable in either the L2 or adult stages. Using immunogold electron microscopy, GTP-CH was shown to be predominantly localized to the cell body of the body wall muscles and the cells of the intestine in the L3.
Autism (MIM 209850) is a severe neuropsychiatric disorder of unknown aetiology with profound consequences for patients and their families. Strong evidence from twin and family studies indicates the importance of genetic factors in the development of idiopathic autism, although it is clear that these influences are complex. This review focuses on recent molecular investigations to identify susceptibility loci implicated in autistic disorder.
Whereas the standard immunosuppressive agents foster development of posttransplant lymphoproliferative disorders (PTLDs), the impact of RAD, a macrolide with potent immunosuppressive properties, and other immunosuppressive macrolides on these disorders remains undetermined. We found that RAD had a profound inhibitory effect on in vitro growth of six different PTLD-like Epstein-Barr virus+ lymphoblastoid B cell lines. Similar to normal T cells, RAD blocked cell-cycle progression in PTLD-like B cells in the early (G(0)/G(1)) phase. Furthermore, RAD increased the apoptotic rate in such cells. The drug also had a profound inhibitory effect on the growth of PTLD-like Epstein-Barr virus+ B cells xenotransplanted s.c. into SCID mice. The degree of the RAD effect varied among the three B cell lines tested and was proportional to its effects on the cell lines in vitro. In this in vivo xenotransplant model, RAD markedly delayed growth or induced regression of the established tumors. In one line, it was able to eradicate the tumor in four of eight mice. When RAD treatment was initiated before tumor cell injection, a marked inhibition of tumor growth was seen in all three lines. In two of them, the drug prevented tumor establishment in approximately 50% of mice (5/11 and 5/8). In summary, RAD is a potent inhibitor of PTLD-like cells in vitro and in vivo. These findings indicate that, in contrast to the standard immunosuppressive agents, macrolides such as RAD may be effective in prevention and treatment of PTLDs.
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A group of 103 subjects with a strict diagnosis of autism were tested for deletion of band q11.2 on the long arm of chromosome 22. No deletions were found, indicating that when a patient has been diagnosed with autism using strict and consistent criteria, in the absence of other indications, it is unlikely that this individual will have a 22q11 deletion. Testing for 22q11 deletions is therefore unlikely to be necessary in these patients. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:15-17, 2000.
Sociocultural factors during the postcolonial period have been implicated as paramount in generating conditions that promoted both the origin and subsequent epidemic spread of HIV-1 in Africa. We suggest, however, that the origin of the disease may lie in the interaction between colonial practices (e.g., labor camps, nonsterile vaccination campaigns) and traditional bushmeat hunting in French Equatorial Africa. Both the epidemiology of HIV-2 and the colonial history of West Africa appear more complex, but similar conditions existed there and may have contributed to the origin of HIV-2. Focusing the search for the origins of HIV-1 and HIV-2 on this earlier time period may contribute to understanding the evolution of the HIV viruses and the dynamics of emerging diseases.
We have developed a multislice protocol for quantitative T1 measurements in which the processing time and the acquisition time are under 2 minutes each for a complete brain study of 15 slices. An echoplanar, inversion-recovery image sequence is designed to collect data suitable for analysis using a linear regression algorithm. The precision is approximately twice the noise to signal ratio of the images. The accuracy of the protocol is better than 1% for T1 in the range 0-2 seconds and deviates slightly for longer T1 values. The protocol is insensitive to B1 field values. If needed, the data can be postprocessed using a slow, nonlinear algorithm to give an accuracy of less than 1% and a precision of approximately the noise to signal ratio throughout a range of T1 values from 0 to 4 seconds.
Haplotypes derived from five polymorphic restriction sites were determined in 50 Carrier-Sekani and 70 Mvskoke chromosomes, and the results were integrated with those previously obtained for 11 South American Indian populations. Eleven haplotypes were identified in the Mvskokes, while five were observed in the Carrier-Sekani. As in South American natives, haplotype 2 (+----) and 6 (-++ -+) were the most prevalent among the Mvskoke (46% and 30%, respectively). In the Carrier-Sekani, haplotype 2 was also the most common, but haplotype 5 (-+ -++) was somewhat more frequent (18%) than 6 (12%). High heterozygosities, as well as genetic differentiation, were observed among these two North American and two other South American groups (Mapuche and Xavante). They could be due to non-Indian admixture in the Mvskoke and Mapuche, but the findings in the other two populations require some other type of explanation.
A population of Formosan macaques at Mt. Longevity exhibits an unusually high incidence of supernumerary nipples (polythelia: between 1-6 accessory nipples and/or areolae on 33% of adults), as well as a high rate of twinning (about 1% of births). The coexistence of these unusual traits suggests a connection, which is further supported by a tendency for mothers of twins to have accessory nipples and for twins to be born in troops with high incidence of polythelia.
BACKGROUND: Endometriosis is a major women's health-care problem. It causes pain and/or infertility, and affects millions of women worldwide. Endometriosis is defined according to histological criteria by the presence of tissue resembling endometrium in sites outside the uterus, most commonly the ovaries and peritoneum. The aim of treatment has been to remove the deposits of ectopic endometrium that are thought to be responsible for the symptoms of endometriosis. This can be achieved surgically by destroying or removing the implants; medical therapies induce atrophy within the hormonally-dependent ectopic endometrium. The duration of hormonal treatment may be limited by unwanted side effects. There is some evidence, however, from epidemiological research that current use of the combined oral contraceptive pill (OCP) is associated with a reduced incidence of endometriosis. The combined pill has the great advantage over other hormonal treatments that it can be taken indefinitely. OBJECTIVES: The aim of this review was to establish the role of modern oral contraceptives in the management of painful symptoms ascribed to endometriosis. SEARCH STRATEGY: The search strategy of the Menstrual Disorders Group was utilised to identify all randomised trials of the use of oral contraceptives in the treatment of symptomatic endometriosis. In addition a search of the Cochrane Controlled Trials Register was undertaken together with approaches to pharmaceutical companies. SELECTION CRITERIA: All truly randomised controlled trials of the use of oral contraceptive pills in the treatment of women of reproductive age with symptoms ascribed to the diagnosis of endometriosis made visually at a surgical procedure, were included. DATA COLLECTION AND ANALYSIS: Study quality assessment and data extraction was carried out independently by two reviewers. One of the assessors was an expert in the content matter. MAIN RESULTS: Only one study was identified which satisfied the inclusion criteria. The oral contraceptive used in a conventional manner was less effective than a GnRH analogue in the relief of dysmenorrhoea. No significant difference was noted between the effectiveness of the oral contraceptive pill and a GnRH analogue in the relief of dyspareunia or non-menstrual pain. Headaches and weight gain were more commonly associated with oral contraceptive usage than with GnRH analogue usage whereas hot flushes, insomnia and vaginal dryness were less common. REVIEWER'S CONCLUSIONS: There is a paucity of data relating to the use of oral contraceptive preparations in the treatment of symptomtic endometriosis. The data such as it is supports the common practice of the use of the oral contraceptive pill as a first line therapy but further research is required to fully evaluate its role in the management of endometriosis.
The novel glycolipid RC-552 shares common structural features with the natural products lipid A and the previously described cardioprotectant monophosphoryl lipid A. RC-552 administered to dogs as a bolus intravenous dose (35-70 microg/kg) either 24 h or 10 min prior to 60 min of regional myocardial ischemia and 3 h of reperfusion significantly (P<0.05 v control) reduced infarct size (IS) as assessed by triphenyltetrazolium staining from 27.0+/-2.3% of the area-at-risk (AAR) to 13.3+/-2.2% and 15.0+/-3.0%, respectively. Administration of the non-specific inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine (30 mg/kg, subcutaneously) 1 h prior to ischemia blocked the ability of RC-552 (35 microg/kg, 24 h pretreatment) to reduce infarct size. Intravenous pretreatment with RC-552 (35 microg/kg) either 24 h or 10 min prior to five 5 min repetitive cycles of ischemia and reperfusion significantly improved regional myocardial segment shortening (percentage of control) at all time points during 2 h of reperfusion in dogs. These effects of RC-552 in either cardiac injury model occurred independent of differences in AAR, transmural blood flow during ischemia or hemodynamics throughout the experiment. In contrast with monophosphoryl lipid A (MLA), which has also been reported to be cardioprotective at similar doses in dogs, RC-552 was approximately 100 times less prone to cause fever in the USP rabbit pyrogen test. Likewise, RC-552 did not induce secretion of the proinflammatory cytokines TNF, IL-6 or IL-8 from THP-1 cells or alter the expression of adhesion molecules on human neutrophils at concentrations up to 10 microg/ml. MLA was active in these systems at concentrations in the range 0.1-1.0 microg/ml. In conclusion, RC-552 reduces myocardial infarct size and stunning in dogs in the absence of residual immunomodulatory activity.
The contrast-detail characteristic of a display system is a powerful tool for evaluating displayed image quality. It takes into account the physical properties of the display, the psychophysical aspects of the observer, and the viewing conditions. It is a more sensitive measurement of the displayed image quality than a simple Society of Motion Picture and Television (SMPTE) pattern. Yet, it is relatively simple to measure and requires no special equipment or analysis tools. In this presentation, the results of the evaluation of several cathode ray tube (CRT) monitors and a digital projector will be presented. Contrast-detail characteristics of these display devices were measured under various gamma and display settings. The results show excellent intraobserver and interobserver variance (<1 step on the grayscale). Extraneous light, such as room lighting, affects the contrast threshold more severely at low background levels more than at high background. Gamma settings on graphics adapters affect the shapes of the contrast-detail curve for all display types. Gamma settings of approximately 2.0 result in a better contrast threshold for both high and low background brightness. The results show complex differences in contrast-detail characteristics for different display types. The digital projector display not only has significantly worse performance than CRT monitors, but also is affected more by extraneous light. High-brightness monitors with optimal monitor and graphics adapter settings have better performance than color or low-brightness monitors. However, under some settings, the performance of high-brightness monitors is not always better at all object sizes and background levels.