Search PubMed⌕ Search

Biomedical subjects

A Silver

Publications and source records attributed to A Silver.

At least 37 records · Page 2Linked to original sources
PubMed1996

Iron intake and the risk of colorectal cancer.

Prospectively gathered data from the National Health and Nutrition Examination Survey I and the National Health Evaluation Follow-Up Study were analyzed to evaluate the risk of colorectal cancer due to consumption of iron. Morbidity and mortality data due to colorectal cancer were available on 14,407 persons first interviewed in 1971 and followed through 1986. A total of 194 possible colorectal cancers occurred in this group over the 15-year period. Subsite analysis showed that the risk of colon cancer due to iron intake was elevated throughout the colon for both men and women, with the highest adjusted risks for the interquartile range seen in the proximal colon for females (relative risk, 1.51; 95% confidence interval, 1.41-1.60). The risk of rectal cancer was not significantly elevated for men or women. Elevated serum iron was also associated with increased risk; however, this effect was strongest in the distal (rather than proximal) colon and was significant only among females (adjusted relative risk, 1.73; 95% confidence interval, 1.03-2.92). The mean transferrin saturation was higher among cases than controls (30.7 versus 28.7%), but total iron-binding capacity did not seem to predict the occurrence of colorectal cancer. Proportional hazards models confirmed that the effects of iron and serum iron were not confounded by age, gender, energy consumption, fat intake, or other known risk factors for colorectal cancer. These data suggest that iron may confer an increased risk for colorectal cancer, and that the localization of risk may be attributable to the mode of epithelial exposure. It seems that luminal exposure to iron increases risk proximally, whereas humoral exposure increases risk distally. These differences may be due to such factors as oxidation state, binding proteins and the presence of other cofactors such as bile acids, products of bacterial metabolism.

Adult↗
PubMed1994

The 1993 Walter Hubert Lecture: the role of the p53 tumour-suppressor gene in tumorigenesis.

The p53 tumour-suppressor gene is mutated in 60% of human tumours, and the product of the gene acts as a suppressor of cell division. It is thought that the growth-suppressive effects of p53 are mediated through the transcriptional transactivation activity of the protein. Overexpression of the p53 protein results either in arrest in the G1 phase of the cell cycle or in the induction of apoptosis. Both the level of the protein and its transcriptional transactivation activity increase following treatment of cells with agents that damage DNA, and it is thought that p53 acts to protect cells against the accumulation of mutations and subsequent conversion to a cancerous state. The induction of p53 levels in cells exposed to gamma-irradiation results in cell cycle arrest in some cells (fibroblasts) and apoptosis in others (thymocytes). Cells lacking p53 have lost this cell cycle control and presumably accumulate damage-induced mutations that result in tumorigenesis. Thus, the role of p53 in suppressing tumorigenesis may be to rescue the cell or organism from the mutagenic effects of DNA damage. Loss of p53 function accelerates the process of tumorigenesis and alters the response of cells to agents that damage DNA, indicating that successful strategies for radiation therapy may well need to take into account the tissue of origin and the status of p53 in the tumour.

Animals↗
PubMed1994

Rurality and tuberculosis incidence trends in North and South Carolina, 1980 to 1992.

U.S. tuberculosis incidence rates increased steadily from 1985 through the end of 1992. Many factors have been implicated as contributors to the reversal in the historic decline of tuberculosis: the HIV epidemic, poverty and homelessness, immigration from less developed countries, and a deteriorating public health infrastructure. The purposes of this study were to demonstrate the extent of geographic variation in tuberculosis incidence rate trends in North and South Carolina and to quantify the association between aggregate-level characteristics of state economic areas and incidence rate trends. Data were obtained from the U.S. 1980 and 1990 decennial census and from the North and South Carolina health departments. In North Carolina, tuberculosis trends declined rapidly in the early 1980s, but declined much less rapidly from 1986 to 1992. In South Carolina, tuberculosis trends were nearly static during the early 1980s, but declined rapidly from 1986 to 1992. Rural and high-poverty state economic areas in South Carolina experienced especially favorable changes in tuberculosis incidence trends. South Carolina has a unique tuberculosis control program that makes widespread use of enablers, incentives, and directly observed therapy. This study demonstrates the distinct tuberculosis incidence trends that existed in two contiguous states and suggests that approaches to tuberculosis control that improve access to care may be effective in improving tuberculosis incidence trends, particularly in poor and rural areas. Strengthening tuberculosis programs may be an important strategy for controlling the current resurgence of tuberculosis in the United States.

Cohort Studies↗
PubMed1993

Uptake of cystic fibrosis testing in primary care: supply push or demand pull?

OBJECTIVE: To determine the acceptability and feasibility of screening for carriers of cystic fibrosis in a primary care setting. DESIGN: Follow up study over 15 months of patients offered carrier testing by mouthwash. SETTING: A general practice in inner London. SUBJECTS: 5529 patients aged 18-45 invited by various methods and combinations of methods (letter, booklet, personal approach) for testing. MAIN OUTCOME MEASURES: Uptake of screening, anxiety, and knowledge of test. RESULTS: 957 (17%) invitees were screened over the 15 months. 28 carriers and no carrier couples were detected. Uptake rates were 12% (59/502 patients) among patients invited by letter and tested by appointment; 9% (47/496) among patients invited by letter, with leaflet, and tested by appointment; 4% (128/2953) among patients invited by letter six weeks before the end of the study and tested by appointment; 17% (81/471) among patients offered passive opportunistic testing; 70% (453/649) among patients offered active opportunistic testing; and 25% (22/88) among patients offered active opportunistic testing by appointment. A short term rise in anxiety among those given a positive test result had dissipated by three months. At three months about one fifth and one third of those given positive and negative results respectively did not understand their results correctly. CONCLUSION: These results suggest that the strongest variable in determining uptake of screening is the active approach by a health professional offering immediate testing. It remains to be resolved whether the high uptake rates achieved by active recruitment indicate a supply push for this new test rather than a demand from the population.

Adolescent↗
PubMed1993

Telomere-like DNA polymorphisms associated with genetic predisposition to acute myeloid leukemia in irradiated CBA mice.

There is evidence that interstitial telomere (TTAGGG)n-like sequences at chromosome 2 fragile sites play an important role in the somatic events that characterize the earliest phases of radiation-induced acute myeloid leukemia in the CBA/H mouse. Here we show that the highly inbred CBA/H colony unexpectedly contains four genotypic variants for telomere-like sequence arrays and that almost all induced myeloid leukemias derive from one of the variant subpopulations that constitutes approximately 20% of the colony. Preliminary evidence on the irregular inheritance patterns for these variant sequences is discussed together with the proposal that one form of these telomere sequence arrays either represents or is closely linked to a locus that influences chromosome 2 breakage patterns in hemopoietic cells following irradiation and, through this, susceptibility to induced myeloid leukemia.

Acute Disease↗
PubMed1993

The role of DNA repeats and associated secondary structures in genomic instability and neoplasia.

Tumour-associated genetic changes frequently involve DNA translocation or deletion. Many of these events will have arisen from initial genomic damage, induced by either the activity of endogenous metabolic processes or from exposure to environmental genotoxic agents. Although initial genomic damage will have been widely distributed, tumorigenic events are confined to certain DNA target sites. Furthermore, within these target sites there appear to be regions of preferential DNA rearrangement, and examination of these sites implies that the location and extent of such rearrangement may be influenced by DNA primary and secondary structure rather than simply by the point of damage. We selectively review evidence relating to DNA structures that may predispose certain regions of the genome to damage-induced rearrangement, and discuss the possible role of interstitial, inverted telomere-like sequence arrays in promoting chromosomal events of a type known to be associated with some human and animal tumours.

Animals↗
PubMed1993

Murine radiation myeloid leukaemogenesis: relationship between interstitial telomere-like sequences and chromosome 2 fragile sites.

While the specific nature of chromosomal fragile sites and their relationship to human leukaemogenesis remain obscure, there is evidence that chromosomal fragility may, in some circumstances, be associated with telomere-like repeat sequences and that chromosome 2 fragility in the mouse is involved in the initiation of myeloid leukaemia by ionising radiation. Here we describe the molecular cloning and characterisation of two murine telomere-like sequences, one having an inverted repeat structure and the other a simple tandem repeat organisation. The inverted telomere repeat clone generates an in situ chromosome 2 hybridisation pattern very similar to the distribution of the radiation-sensitive fragile sites previously found to be associated with leukaemogenic initiation. Furthermore, statistical comparison of the distributions of radiation induced breakpoints and sites of inverted telomere repeat hybridization indicates concordance at all chromosome 2 sites excluding the terminal regions. These data are discussed with respect to mechanisms of radiation-induced, site-specific chromosome 2 rearrangement and their implications for leukaemogenic initiation.

Acute Disease↗
PubMed1992

Clinical results of piezoelectric gallstone lithotripsy.

The safety and efficacy of piezoelectric extracorporeal shockwave lithotripsy in the treatment of symptomatic gallbladder stones were evaluated in 53 consecutively treated patients. All treatments were performed as outpatients without anesthesia; over 95 per cent of 109 treatments were performed without analgesia or sedation. Ursodeoxycholic acid was administered post-treatment. Seventy per cent of patients had multiple sessions. Cumulative stone-free rates of 38 per cent at 6 months, 65 per cent at 12 months, and 75 per cent at 15 months were achieved. There was no difference in eventual stone clearance between patients with single stones less than 20 mm diameter, single stones greater than or equal to 20 mm diameter, or multiple (two or three) stones, although patients with single smaller stones required significantly fewer total shocks to become stone-free (P = .02). Stone clearance correlated with estimated stone volume. Biliary pain occurred in 62 per cent of patients after treatment but ceased in stone-free patients. Biliary complications of pancreatitis (7.5%) and choledocholithiasis (3.8%) were successfully treated by endoscopic papillotomy. Nonbiliary complications were virtually nonexistent. Three patients (5.7%) had elective cholecystectomy. Results indicate that piezoelectric lithotripsy is a safe, minimally painful treatment that, in conjunction with oral bile acids, can produce stone-free rates of 75 to 100 per cent in selected patients.

Adult↗
PubMed1991

DNA methylation changes in the IL-1 (2F) chromosomal region of some radiation-induced acute myeloid leukaemias carrying chromosome 2 rearrangements.

Acute myeloid leukaemias (AML) arising in irradiated CBA/H mice frequently have breakpoints in the F region of chromosome 2. The closely linked cytokine genes interleukin (IL)-1 alpha and beta map to this region, and the beta gene is deregulated in some AMLs. Using pulsed-field gel electrophoresis techniques, we show here that an 800 kb 2F region encoding IL-1 alpha and beta is not obviously rearranged in six leukaemias carrying chromosome 2 abnormalities. However, changes in IL-1 region DNA methylation in three leukaemias may be consistent with loss of hypermethylated sequences from one chromosome copy. These possible 2F region losses are discussed in relation to genomic imprinting and its potential role in murine myeloid leukaemogenesis.

Acute Disease↗
PubMed1991

Case report 696: Chondroblastoma of the right acetabulum and superior pubic ramus.

A case of chondroblastoma involving the right acetabulum and superior pubic ramus in a 60-year-old man has been presented. Tissue was obtained by open biopsy. The clinical and radiographic characteristics of chondroblastoma in general, and this tumor in particular, were discussed. The histopathology and differential diagnosis were also considered. The relatively uncommon site of the tumor and its occurrence in an older patient made the radiographic diagnosis difficult, and other possibilities were discussed.

Acetabulum↗
PubMed1991

Development of faculty consultants in a problem-based third year community medicine clerkship.

This paper describes the development of consultancy groups in behavioral science, epidemiology and biostatistics, and information science in a required community medicine rotation with a twenty year history. The addition of consultants to individual student tutors and field preceptors has led to a structure which promotes student-project flexibility, development of critical assessment skills and independent learning while maximizing faculty expertise and effectiveness.

Behavioral Sciences↗
PubMed1991

Renal insufficiency and secondary hyperparathyroidism in elderly patients.

Glomerular filtration rate (GFR) is frequently reduced in elderly people. However, the effect of this on mineral metabolism in this population has received little attention. GFR, serum intact parathyroid hormone (PTH) and vitamin D metabolites were measured in 37 patients admitted to hospital for various reasons. In 20 patients with GFR greater than 50 mL/min, an elevated serum intact PTH concentration (greater than 5.4 pmol/L) was found in two, while in 17 patients with GFR less than 50 mL/min PTH was elevated in 13. One of this group was hypercalcaemic and presumed to have primary hyperparathyrodism. Adjusted calcium was normal in all other patients. Two patients had a low serum 25-hydroxyvitamin D concentration (less than 9 nmol/L) suggesting vitamin D insufficiency while a further five had a reduced 1,25-dihydroxyvitamin D concentration, four of these having a GFR less than 50 mL/min. We conclude that hyperparathyrodism is common in hospitalized elderly patients, particularly in those with mild to moderate renal insufficiency. This may contribute to bone mineral loss in such patients.

Aged↗