Nonsteroidal anti-inflammatory drug-associated dyspepsia: basic mechanisms and future research.
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Biomedical subjects
Publications and source records attributed to J Jones.
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BACKGROUND: Decision aids are interventions designed to help people make specific and deliberative choices among options (including status quo) by providing (at a minimum) information on the options and outcomes relevant to a person's health status. A systematic review is needed to summarize what is known about their efficacy. OBJECTIVES: 1. To create an inventory of existing decision aids. 2. To conduct a systematic review of randomized controlled trials of decision aids aimed at improving people's decision making and outcomes. SEARCH STRATEGY: The following electronic databases were searched: MEDLINE, EMBASE, PsycINFO, CINAHL, Aidsline, Cancerlit, the Cochrane Controlled Trials Register. In addition, individuals known to be active in the field of decision support were contacted. SELECTION CRITERIA: We screened titles and abstracts for all interventions providing structured, detailed, and specific information on treatment or screening options and outcomes to aid decision making. Information about the decision aids was compiled in an inventory and those evaluated in a randomized controlled trial were reviewed in detail. DATA COLLECTION AND ANALYSIS: Using Cochrane review methods, two reviewers independently screened and extracted data on several evaluation criteria. Results of randomized trials were pooled using weighted mean differences and relative risks with all data analysed using a random effects model. MAIN RESULTS: Eighty-seven decision aids were identified. Twenty-three of them had been evaluated in 24 randomized controlled trials. Among the trials comparing decision aids to usual care interventions, decision aids performed better in terms of: a) greater knowledge of options in seven of seven studies (weighted mean difference (WMD = 19 out of 100, 95% confidence interval (CI): 13,25); b) more realistic expectations in two of three studies (RR=1.48 95%CI 1.02, 2.14); c) lower decisional conflict related to feeling informed in three of three studies (WMD = -9.0 of 100 95%CI: -15, -3); d) reducing the proportion of people who were passive in decision making in three of four studies (RR = 0.63, 95% CI: 0.5, 0.8). When simpler decision aids were compared to more detailed ones, the relative improvement was significant in: a) improved knowledge in two of seven studies (WMD = 4 out of 100, 95% CI: 2, 5); b) realistic expectations in two of two studies (relative risk (RR ranged from 1.5 95%CI: 1.3,1.8); and c) decisional conflict in one of two studies (WMD= -4 95% CI -8,-0.2). There was a consistent trend for decision aids to do no better than comparison interventions in affecting: satisfaction with the decision in five of six studies, satisfaction with the decision making process in four of five studies, and anxiety in four of five studies. Decision aids had a variable effect on which screening or treatment options were selected. Exposure to decision aids relative to controls resulted in a consistent non-significant trend toward reduced preference for major surgery over conservative options by 21 to 42 per cent in five of five studies; however, they had no impact on circumcision in two of two studies. For colon and prostate cancer screening choices, the results were inconsistent. Two studies have shown no impact on persistence with chosen option and few studies have shown significant benefits on general health outcomes (two of three studies), or disease-specific health outcomes (one of four studies). REVIEWER'S CONCLUSIONS: The number of decision aids is expanding, but there is considerable overlap in some areas leaving gaps in others. Trials of decision aids indicate that they are superior to usual care interventions in improving knowledge and realistic expectations of the benefits and harms of options; reducing passivity in decision making; and lowering decisional conflict stemming from feeling uninformed. When simpler versions of decision aids are compared to more detailed aids, the differences in knowledge are marginal but there are other benefits in terms of creating realistic expectations and in reducing decisional conflict. To date, decision aids have had little effect on anxiety or satisfaction with the decision making process or satisfaction with the decision. Their effects on choices vary with the decision. The effects on persistence with chosen therapies and health outcomes require further evaluation. The essential elements in decision aids for different groups and different types of decisions need to be established. Consensus needs to be reached regarding standards for developing and evaluating decision aids.
Two recent case-control studies have suggested a strong association of a missense polymorphism in exon 2 of the cathepsin D gene (CTSD) and Alzheimer disease (AD). However, these findings were not confirmed in another independent study. We analyzed this polymorphism in two large and independent AD study populations and did not detect an association between CTSD and AD. The first sample was family-based and included 436 subjects from 134 sibships discordant for AD that were analyzed using the sibship disequilibrium test (SDT, p = 0.68) and the sib transmission/disequilibrium test (Sib-TDT, p = 0.81). The second sample of 200 AD cases and 182 cognitively normal controls also failed to show significant differences in the allele or genotype distribution in cases versus controls (chi2, p = 0.91 and p = 0.88, respectively). In addition, two-point linkage analyses in an enlarged family sample (n = 670) did not show evidence for linkage of the chromosomal region around CTSD. Thus, our analyses on more than 800 subjects suggest that if an association between the CTSD exon 2 polymorphism and AD exists, it is likely to be smaller than previously reported.
Abnormalities of the growth hormone (GH)/ insulin-like growth factor (IGF) axis have been reported in children with chronic renal failure (CRF) and post-transplant, and are thought to contribute to poor growth. This study examined the effect of CRF and steroid therapy (given post-transplant and to children with normal renal function) on the GH-IGF axis in children with normal and abnormal growth. Thirty-one children with CRF, ten on dialysis, 26 with renal transplants and ten taking steroid therapy but with normal renal function, were studied. IGF-I, measured by radioimmunoassay, was normal but IGF bioactivity was low in groups with a decreased glomerular filtration rate (P<0.05). Transplanted children growing at a subnormal growth rate had lower IGF bioactivity than those growing at a normal rate (P=0.03), but there was no such difference in bioactivity in children with CRF. There was no correlation between IGF bioactivity and prednisolone treatment. There was no correlation between IGF binding proteins 1, 2 or 3 and growth.
Chronicity following hepatitis B virus (HBV) infection may be maintained by high levels of viral proteins circulating in the serum. To examine the characteristics of T cells capable of co-existing with the secreted hepatitis B e-antigen (HBeAg), T-cell receptor (TCR) transgenic (Tg) mice were produced. To insure that HBeAg-specific T cells would not be deleted in the presence of serum HBeAg, the TCR alpha and beta-chain genes used to produce the TCR-Tg mice were derived from T-cell hybridomas from HBeAg-Tg mice. A TCR-Tg lineage (11/4-12) was produced that possessed a high frequency (approximately 67%) of CD4(+) T cells that expressed a TCR-Tg specific for the HBeAg. As predicted, when 11/4-12 TCR-Tg mice were bred with HBeAg-Tg mice no deletion of the HBeAg-specific CD4(+) T cells occurred in the thymus or the spleen. Functional analysis of the TCR-Tg T cells revealed that the HBeAg-specific CD4(+) T cells escaped deletion in the thymus and periphery by virtue of low avidity. Regardless of their low avidity, HBeAg-specific TCR-Tg T cells could be activated by exogenous HBeAg as measured by cytokine production in vitro and T-helper cell function for anti-HBe antibody production in vitro and in vivo. Furthermore, activated TCR-Tg HBeAg-specific T cells polarized to the Th(1) subset were able to elicit liver injury when transferred into HBeAg or HBcAg-Tg recipients. Therefore, HBeAg-specific CD4(+) T cells that can survive deletion or anergy in the presence of circulating HBeAg nonetheless are capable of being activated and of mediating liver injury in vivo.
Functional magnetic resonance imaging (fMRI) was requested to assist in the evaluation of a comatose 38-year-old woman who had sustained multiple cerebral contusions from a motor vehicle accident. Previous electrophysiologic studies suggested absence of thalamocortical processing in response to median nerve stimulation. Whole-brain fMRI was performed utilizing visual, somatosensory, and auditory stimulation paradigms. Results demonstrated intact task-correlated sensory and cognitive blood oxygen level dependent (BOLD) hemodynamic response to stimuli. Electrodiagnostic studies were repeated and evoked potentials indicated supratentorial recovery in the cerebrum. At 3-months post trauma the patient had recovered many cognitive & sensorimotor functions, accurately reflecting the prognostic fMRI evaluation. These results indicate that fMRI examinations may provide a useful evaluation for brain function in non-responsive brain trauma patients.
Reports in the literature indicate that the trifunctional amino acid D-penicillamine (D-P) induces a variety of muscle abnormalities, although the mechanisms are unknown. We hypothesised that defects may also arise due to the effects of D-P on rates of protein synthesis, possibly via changes in muscle metal composition. Male Wistar rats were injected with D-P at doses of 50 and 500 mg/kg body weight, i.p. Rats designated as controls were injected with 0.15 mol/l NaCl. After 24 h, there were reductions in muscle protein contents, protein synthetic capacities (RNA:protein ratio), fractional rates of protein synthesis, synthesis rates per unit RNA and synthesis rates per unit DNA in skeletal muscles of D-P treated rats. There were no statistically significant differences between the responses of the muscles containing a predominance of either Type I (represented by the soleus) or Type II (represented by the plantaris) fibres. In general, intracellular amino acids were not significantly affected by D-P treatment. Changes in muscle metals included significant reductions in copper, iron and manganese, without alterations in zinc or magnesium. In liver D-P reduced copper and iron though zinc, manganese and magnesium were unaffected. These effects of D-P on muscle may have been direct, as plasma indices of liver (activities of alkaline phosphatase and alanine aminotransferase) and kidney (urea, creatinine and electrolytes) damage were not significantly altered by D-P treatment. Plasma levels of corticosterone, insulin and free T3 were also not significantly affected by D-P treatment. Muscle protein carbonyl concentrations, an index of free radical activity, were similarly unaffected. This is the first report of reduced rates of muscle protein synthesis in D-P treatment. Our data suggests that the reduced rates of muscle protein synthesis may contribute to, or reflect, the muscle abnormalities observed in patients undergoing D-P treatment.
BACKGROUND: Docetaxel and gemcitabine are active against chemotherapy-pretreated non-small-cell lung cancer (NSCLC). The purpose of this phase II study was to evaluate the efficacy and safety of monthly docetaxel combined with weekly gemcitabine in NSCLC patients failing one prior regimen. PATIENTS AND METHODS: Forty patients were enrolled. Prior chemotherapy was a platinum-based combination in 36 patients, using vinorelbine in 26 patients and etoposide in 10 patients. The other four patients had prior single agents. Tumors were refractory or resistant to front-line therapy in 80% of patients. Treatment was gemcitabine 800 mg/m2 days 1, 8, 15 and docetaxel 100 mg/m2 day 1, with cycles repeated every four weeks. RESULTS: Thirteen patients responded (32.5%; 95% confidence interval (CI): 19%-49%), including one complete and 12 partial responses. Responses were observed at all metastatic sites, with similar response frequencies in platinum-sensitive and platinum-resistant/refractory tumors. The median time to progression for responders was nine months, with two responses lasting longer than a year. Median survival was 8.1 months. Hematologic toxicities included grade 4 neutropenia in 23 patients, with 4 episodes of febrile neutropenia, grade 3-4 thrombocytopenia in 9 patients, and anemia requiring red cell transfusions in 9 patients. With the exception of asthenia, severe non-hematologic toxicities were infrequent. CONCLUSIONS: Monthly docetaxel, combined with weekly gemcitabine, is an active and safe second-line therapy for NSCLC patients.
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BACKGROUND: Docetaxel and gemcitabine are active against breast cancer. The purpose of this phase II study was to evaluate the efficacy and safety of monthly docetaxel combined with weekly gemcitabine in patients with chemotherapy-pretreated metastatic breast cancer. PATIENTS AND METHODS: Thirty-nine patients were enrolled, of whom thirty had received prior chemotherapy in the adjuvant setting, seven for metastatic disease, and two for both, including prior anthracycline in 33 patients. Treatment was gemcitabine 800 mg/m2 days 1, 8, 15 and docetaxel 100 mg/M2 on day 1, with cycles repeated every four weeks. RESULTS: Response rate was 79% (95% confidence interval (CI): 63%-91%), with 2 complete and 29 partial responses. Twenty-five of the responders remained progression-free for more than six months. Median survival was 24.5 months. Delivered dose intensity of gemcitabine was lower than expected (63% of planned). The predominant hematologic toxicity was grade 4 neutropenia in 36 patients, complicated by fever in three patients. With the exception of asthenia, severe non-hematological toxicities were infrequent. CONCLUSIONS: Monthly docetaxel, combined with weekly gemcitabine, has significant but manageable hematologic toxicity. Despite frequent dose adjustments, this doublet is very active in metastatic breast cancer, producing a high proportion of durable responses associated with favorable survival.
Four sialic acid-rich (SA-rich) proteins found in bone and dentin, osteopontin (OPN), bone sialoprotein (BSP), bone acidic glycoprotein-75 (BAG-75), and dentin matrix protein 1 (DMP1), share some common features. We used SDS-PAGE and Western immunoblots to analyze and compare SA-rich proteins in bone and dentin extracts from rats with a single chromatographic procedure. OPN was detected in dentin extracts, with a relative level less than one-seventieth of that in bone. Both bone and dentin BSP demonstrated an extremely broad distribution pattern, probably due to a high degree of heterogeneity in post-translational modifications. BAG-75 in both bone and dentin was detected as an 83 kDa band, dramatically distinct from that of DMPI. Using a polyclonal antibody raised against a purified bone 57 kDa protein (a portion of DMPI), we detected 150 kDa protein bands in bone fraction; the same bands were recognized by antirecombinant rat DMPI antibody. Bands from dentin migrating at about 150 kDa in earlier fractions and progressing to 200 kDa in later fractions showed a clear immunoreactivity to the anti-57 kDa antibody. We conclude that the majority of DMPI in rat bone is processed into fragments, whereas that in dentin remains intact.
OBJECTIVE: Circulating insulin-like growth factor (IGF)-II and IGF binding protein-2 (IGFBP-2) are frequently altered, often in parallel, in numerous pathologies including neoplastic disease but little is known about their normal regulation. This study compared serum IGF-II and IGFBP-2 distributions between acromegalics and a large normal adult population to explore possible determinants. PATIENTS: Sixty acromegalic patients undergoing screening colonoscopy (age range 25-81 years); normative data from 306 healthy adults (age range 20-89 years). MEASUREMENTS: Serum IGF-I, IGF-II, IGFBP-2 and IGFBP-3 were measured in healthy adults and acromegalics. Mean growth hormone (GH) levels were obtained for acromegalic patients. Differences were compared using t-tests (unadjusted) and multiple regression models (adjusted for age and gender). Correlations were expressed as Pearson's coefficient (r). RESULTS: For acromegalic patients, GH was significantly correlated with IGF-I (r = 0.50; P < 0.001) and IGFBP-3 (r = 0.29; P = 0.03) but not IGF-II or IGFBP-2. Contrary to expectations, mean IGF-II and IGFBP-2 levels were significantly raised in the acromegalics compared with normals [adjusted mean difference (95% CI) = 226 (181, 271) microg/l and 305 (200, 410) microg/l, respectively]. Ten acromegalic patients had colorectal neoplasia but their presence did not contribute to the elevations in serum IGF-II and IGFBP-2. The (IGF-I + IGF-II)/IGFBP-3 molar ratios were remarkably constant in both healthy adults and acromegalics, but the relationships of the ligands individually with IGFBP-3 were not linear: as IGFBP-3 increased, IGF-I also increased whereas IGF-II initially increased but then decreased. IGFBP-2 did not correlate with IGF-II, but molar concentration significantly correlated with the IGF-II/IGFBP-3 molar ratio (r = 0.40; P = 0.001). CONCLUSIONS: Serum IGF-II and IGFBP-2 levels were paradoxically elevated in acromegalics, independent of the presence of colorectal neoplasia. The (IGF-I + IGF-II)/IGFBP-3 molar ratio appears to be pivotal in determining IGF-II values, which, in turn, expressed as a ratio of IGFBP-3, is related to IGFBP-2. These observations offer new insights into the regulation of these peptides.
HeartCare is an Internet-based information and support service for patients recovering at home from coronary artery bypass graft (CABG) surgery. The system is designed to meet the nursing challenges in health information to support needs of CABG patients. HeartCare (a) provides information and support, tailored to patients' individual and changing recovery needs during CABG recovery, (b) makes recovery information more accessible for timely use by patients, and (c) extends the scope of nursing services to CABG patients from hospital through home. An ongoing randomized controlled study is underway to evaluate the clinical outcomes of patients' use of the HeartCare system and to examine its acceptance as a usable resource for postCABG patients who have limited previous computer experience.
Endometrial hyperplasia is a common disorder that is now observed with increasing frequency in women treated with hormonal replacement therapy or with tamoxifen. This study was undertaken to determine whether genomic features of various forms of endometrial hyperplasias would allow their classification as a benign, premalignant, or malignant abnormality. Comparative genomic hybridization (CGH) was performed on endometrial glands microdissected by laser capture microscope from 19 archival endometrial samples, comprising 5 normal endometria, 1 polyp, 2 simple hyperplasias, 5 hyperplasias with nuclear abnormalities (atypical hyperplasias), and 4 low-grade and 2 high-grade endometrioid carcinomas, 1 with squamous component (adenoacanthoma). Genomic DNA, extracted from the glands and the squamous component in 1 case, was amplified by degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR) and compared with sex-matched DNA by CGH. No genomic imbalances were observed in the normal samples, the polyp, or the simple hyperplasias. However, in atypical hyperplasia, regardless of the level of cytologic atypia, genomic abnormalities were observed that also occurred in endometrioid carcinomas. Chromosomes 1, 8, and 10 were most often affected. The results are compared with molecular genetic abnormalities recently reported in these lesions. This study strongly suggests that atypical endometrial hyperplasias are closely related to endometrioid carcinoma and should be considered precancerous lesions, contrary to simple hyperplasia, which is a benign disorder. The squamous component of one of the high-grade carcinomas showed genetic abnormalities similar to those of endometrioid carcinoma and therefore does not represent squamous metaplasia but is an integral part of the malignant process.
In boys with familial male-limited precocious puberty, an activating mutation of the luteinizing hormone receptor causes Leydig cell hyperplasia, resulting in excess testosterone production. There are no reports of Leydig cell masses in boys with familial male-limited precocious puberty. We describe a 10-year-old boy with familial male-limited precocious puberty who developed Leydig cell nodules.
The problem of how best to recruit and retain doctors in rural and remote communities has led governments to adopt a range of medical workforce incentives, including retention grants. A comprehensive literature survey suggests that medical workforce retention has been poorly distinguished from other supply issues such as recruitment, and that its determinants and the process leading to retention are poorly understood. Such a knowledge gap is likely to limit the effectiveness of retention incentives. This article reports the results of this literature review, and advances a conceptual framework as the basis for ongoing research and evaluating how best to deliver effective retention interventions.
The suitability of ten diets for the development and reproduction of Franklinothrips orizabensis Johansen, the key natural enemy of Scirtothrips perseae Nakahara, a pest of California grown avocados, was determined in the laboratory. The experimental diets evaluated were: (i) irradiated Ephestia kuehniella Zeller eggs; (ii) irradiated E. kuehniella eggs and avocado pollen; (iii) Tetranychus pacificus McGregor eggs; (iv) T. pacificus eggs and avocado pollen; (v) irradiated E. kuehniella eggs and T. pacificus eggs; (vi) irradiated E. kuehniella eggs, T. pacificus eggs and avocado pollen; (vii) Scirtothrips perseae; (viii) Heliothrips haemorrhoidalis (Bouchè); (ix) avocado pollen; and (x) a young avocado leaf. Franklinothrips orizabensis larvae were unable to develop to adulthood on diets 9 and 10. The remaining eight diets supported complete development of F. orizabensis, but only diets 1, 2, 5, 6, 7 and 8 produced fecund females. On diet 5, F. orizabensis exhibited high larval to adult survivorship (90%), mated females exhibited highest daily and lifetime fecundity, and the progeny of mated females were female biased (53%). Analysis of jackknife estimates of net reproduction (Ro), intrinsic rate of increase (rm), and finite rate of increase (lambda) were all significantly greater for F. orizabensis reared on irradiated E. kuehniella eggs and T. pacificus eggs (i.e. diet 5) than corresponding values for other diets on which female F. orizabensis were able to complete development and reproduce. Incorporation of avocado pollen into diets had an adverse effect on demographic statistics for F. orizabensis, and low quality diets resulted in male biased sex ratios for this predator.