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Biomedical subjects

E Thomson

Publications and source records attributed to E Thomson.

At least 19 recordsLinked to original sources
PubMed2003

Effects of acute liver injury on blood coagulation.

The mechanisms leading to the hemostatic changes of acute liver injury are poorly understood. To study these further we have assessed coagulation and immune changes in patients with acute paracetamol overdose and compared the results to patients with chronic cirrhosis and normal healthy controls. The results demonstrate that in paracetamol overdose coagulation factors (F)II, V, VII and X were reduced to a similar degree and were significantly lower than FIX and FXI (mean levels 0.28, 0.16, 0.13, 0.19, 0.51 and 0.72 IU mL(-1), respectively). In cirrhosis, by contrast, FII, FV, FVII, FIX and FX were equally reduced whilst FXI was lower than the other factors (mean levels 0.64, 0.69, 0.62, 0.60, 0.66 and 0.40 IU mL-1, respectively). FVIII was raised in paracetamol overdose patients but normal in those with cirrhosis (mean levels 1.95 and 1.01 IU mL(-1), respectively). Interleukin-6 and tumor necrosis factor-alpha levels were raised in both patient groups, but higher levels were found in paracetamol overdose, compared to cirrhosis. Thrombin-antithrombin and soluble tissue factor levels were higher in those with acute liver injury but normal in cirrhosis. Antithrombin levels were reduced in both acute liver injury and cirrhosis. From these data we put forward a novel mechanism for the coagulation changes in acute paracetamol induced liver injury. We propose that immune activation leads to tissue factor-initiated consumption of FII, FV, FVII and FX, but that levels of FIX and FXI are better preserved because antithrombin inhibits the thrombin induced positive feedback loop that activates these latter factors.

Acetaminophen↗
PubMed2001

Targeted intra-operative radiotherapy (Targit): an innovative method of treatment for early breast cancer.

INTRODUCTION: We believe that conservative treatment of early breast cancer may not require radiotherapy that encompasses the whole breast. We present here the clinico-pathological basis for this view, as well as a novel therapeutic approach that allows intra-operative radiotherapy to be safely and accurately delivered to the target tissues in a standard operating theatre. THE RATIONALE: Whole-organ analysis of mastectomy specimens reveals that 80% of occult cancer foci are situated remote from the index quadrant. In contrast, over 90% of local recurrences after breast conservative therapy occur near the original tumour, even when radiotherapy is not given. Therefore, the remote occult cancer foci may be clinically irrelevant and radiotherapy to the index quadrant alone might be sufficient. A NOVEL TECHNIQUE: The Photon Radiosurgery System (PRS) is an ingenious portable electron-beam driven device that can typically deliver intra-operative doses of 5-20 Gy, respectively, to 1 cm and 0.2 cm from the tumour bed over about 22 min. The pliable breast tissue--the target--wraps around the source, providing perfect conformal radiotherapy. Being soft X-rays, the dose attenuates rapidly (alpha approximately 1/r3), reducing distant damage. RESULTS: In our pilot study of 25 patients (age 30-80 years, T = 0.42-4.0 cm), we replaced the routine post-operative tumour bed boost with targeted intra-operative radiotherapy. There have been no major complications and no patient has developed local recurrence, although the median follow-up time is short, at 24 months. CONCLUSION: It is safe and feasible to deliver targeted intraoperative radiotherapy (Targit) for early breast cancer. We have begun a randomised trial--the first of its kind--comparing Targit with conventional six-week course of radiotherapy. If proven equivalent in terms of local recurrence and cosmesis, it could eliminate the need for the usual six-week course of post-operative radiotherapy.

Adult↗
PubMed2000

Women, men, and contraceptive sterilization.

OBJECTIVE: To review the social and behavior contexts of decisions about contraceptive sterilization and to analyze factors associated with sterilization choices. DESIGN: Multinomial logit regression of sterilization. PATIENT(S): Various subsamples as appropriate to specific analyses drawn from the 10,847 women interviewed in the 1995 National Survey of Family Growth, and the 5,227 men interviewed in the National Survey of Families and Households. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Tubal sterilization and vasectomy. RESULT(S): Surprisingly high proportions of recent tubal sterilizations were performed on unmarried women: 1 in 3 overall, 1 in 5 among white non-Hispanic women, and 2 in 3 among black women. Sterilization choice among continuously married couples also revealed large differences by race and ethnicity. Parity at the time of the last wanted birth is a major factor affecting sterilization choices, although significant effects were found as well as for a number of other variables, including age differences between spouses, education, and religion. Compared with other regions, the ratio of tubal sterilizations to vasectomies is extremely low in the Western region of the United States. CONCLUSION(S): Analysis of sterilization decisions must be based on time since the completion of childbearing. The findings call attention to the need for measuring variables that mediate observed associations with sterilization outcomes.

Adolescent↗
PubMed2000

The role of quantitative single photon emission computerized tomography (SPECT) in the osseous integration process of dental implants.

OBJECTIVE: To evaluate the integration process of endosseous dental implants by using quantitative bone single photon emission computerized tomography (SPECT). METHODS: Five consecutive patients receiving titanium implants (Astra Tech, Mölndal, Sweden) in the normal edentulous jaw were evaluated by bone SPECT before loading and at regular intervals up to 5 months after loading. Osteoblastic activity at the implant site was compared with activity within the skull (reference) to calculate an osteoblastic activity index (AI). RESULTS: A time activity curve obtained by plotting AI against time over 5 months showed 3 distinct phases of osteoblastic activity: (1) a rise in osteoblastic activity, part of which may reflect postoperative changes, (2) maximum activity about 1 month after implant, and (3) a gradual falloff in the AI, which returned to pre-implant levels at about 4 months. CONCLUSIONS: We conclude that this method offers a simple, reproducible, objective, and physiologic approach to studying the osseous integration process that occurs after endosseous dental implants. In this small series of patients, this osseous integrative process appears to have become established approximately 4 months after loading. This method also has the capability of quantitating bone activity in absolute terms of microCi/gram (microcuries per gram) and can be useful when bone grafting and other surgical procedures are involved.

Dental Implantation, Endosseous↗
PubMed1999

Screening for cystic fibrosis carrier state.

Carrier screening for cystic fibrosis as part of reproductive health care, including prenatal care, is not the standard of practice at this time. However, a recent National Institutes of Health Consensus Development Conference recommended that cystic fibrosis carrier screening should be offered to adults with a family history of cystic fibrosis, partners of individuals with cystic fibrosis, couples planning a pregnancy, and couples seeking prenatal testing. A workshop convened to discuss the implementation of these recommendations concluded that several issues must be resolved before these recommendations can be implemented. This commentary reviews the discussions that occurred and the conclusions that were reached at this workshop. Some of the subjects considered by the workshop participants were: the goals and outcomes of carrier screening; the continuum from making a test available to offering that test; to whom, when, and how cystic fibrosis testing should be offered; laboratory practice and quality assurance; provider and patient education; and insurance issues. The workshop participants concluded that those populations to whom carrier screening should be offered might include individuals and couples in high-risk groups who seek preconception counseling, infertility care, or prenatal care. High-risk groups include individuals of white northern European or of Ashkenazi-Jewish descent, those whose partners have cystic fibrosis, and those with a family history of cystic fibrosis. Before screening can be offered systematically to these individuals or couples, practice guidelines, educational materials for providers and patients, informed-consent protocols, and laboratory standards for testing must be developed.

Consensus Development Conferences, NIH as Topic↗
PubMed1998

Hereditary hemochromatosis: gene discovery and its implications for population-based screening.

OBJECTIVE: To evaluate the role of genetic testing in screening for hereditary hemochromatosis to help guide clinicians, policymakers, and researchers. PARTICIPANTS: An expert panel was convened on March 3, 1997, by the Centers for Disease Control and Prevention (CDC) and the National Human Genome Research Institute (NHGRI), with expertise in epidemiology, genetics, hepatology, iron overload disorders, molecular biology, public health, and the ethical, legal, and social implications surrounding the discovery and use of genetic information. EVIDENCE: The group reviewed evidence regarding the clinical presentation, natural history, and genetics of hemochromatosis, including current data on the candidate gene for hemochromatosis (HFE) and on the ethical and health policy implications of genetic testing for this disorder. CONSENSUS PROCESS: Consensus was achieved by group discussion confirmed by a voice vote. A draft of the consensus statement was prepared by a writing committee and subsequently reviewed and revised by all members of the expert group over a 1-year period. CONCLUSIONS: Genetic testing is not recommended at this time in population-based screening for hereditary hemochromatosis, due to uncertainties about prevalence and penetrance of HFE mutations and the optimal care of asymptomatic people carrying HFE mutations. In addition, use of a genetic screening test raises concerns regarding possible stigmatization and discrimination. Tests for HFE mutations may play a role in confirming the diagnosis of hereditary hemochromatosis in persons with elevated serum iron measures, but even this use is limited by uncertainty about genotype-phenotype correlations. To address these questions, the expert group accorded high priority to population-based research to define the prevalence of HFE mutations, age and sex-related penetrance of different HFE genotypes, interactions between HFE genotypes and environmental modifiers, and psychosocial outcomes of genetic screening for hemochromatosis.

Female↗
PubMed1998

Couple childbearing plans and births in Sweden.

We use data from a nationally representative sample of Swedish couples to estimate effects of partners' childbearing plans on the rate of subsequent childbearing. Only 11% of the couples in this sample expressed plans in opposite directions (plan to have a child versus not to have a child), but 24% had differing levels of certainty about their plans. Of the couples in which both partners said they definitely planned to have another child, 44% had a child within two years. If neither partner planned to have another child, less than 2% of couples had a birth. The figure was 6% if the partners had opposing childbearing plans. Thus, both men and women exerted veto power over further childbearing. Disagreements were equally likely to be resolved in favor of the woman as of the man, and effects of partners' plans on the birth hazard did not depend on the couple's gender arrangements, family ideologies, or marital status. We discuss these results in the context of Sweden's public support for gender equality and for childrearing, its pervasive contraceptive regime, and its high rates of cohabitation. We also argue for the collection of data from partners in future family and fertility surveys.

Adult↗
PubMed1997

Recommendations for follow-up care of individuals with an inherited predisposition to cancer. II. BRCA1 and BRCA2. Cancer Genetics Studies Consortium.

OBJECTIVE: To provide recommendations for cancer surveillance and risk reduction for individuals carrying mutations in the BRCA1 or BRCA2 genes. PARTICIPANTS: A task force with expertise in medical genetics, oncology, primary care, gastroenterology, and epidemiology convened by the Cancer Genetics Studies Consortium (CGSC), organized by National Human Genome Research Institute (previously the National Center for Human Genome Research). EVIDENCE: Studies evaluating cancer risk, surveillance, and risk reduction in individuals genetically susceptible to breast and ovarian cancer were identified using MEDLINE (National Library of Medicine) and from bibliographies of articles thus identified. Indexing terms used were "genetics" in combination with "breast cancer," "ovarian cancer," and "screening," or "surveillance" in combination with "cancer family" and "BRCA1" and "BRCA2." For studies evaluating specific interventions, quality of evidence was assessed using criteria of the US Preventive Services Task Force. CONSENSUS PROCESS: The task force developed recommendations through discussions over a 14-month period. CONCLUSIONS: Efficacy of cancer surveillance or other measures to reduce risk in individuals who carry cancer-predisposing mutations is unknown. Based on expert opinion concerning presumptive benefit, early breast cancer and ovarian cancer screening are recommended for individuals with BRCA1 mutations and early breast cancer screening for those with BRCA2 mutations. No recommendation is made for or against prophylactic surgery (eg, mastectomy, oophorectomy); these surgeries are an option for mutation carriers, but evidence of benefit is lacking, and case reports have documented the occurrence of cancer following prophylactic surgery. It is recommended that individuals considering genetic testing be counseled regarding the unknown efficacy of measures to reduce risk and that care for individuals with cancer-predisposing mutations be provided whenever possible within the context of research protocols designed to evaluate clinical outcomes.

Antineoplastic Agents, Hormonal↗
PubMed1997

Recommendations for follow-up care of individuals with an inherited predisposition to cancer. I. Hereditary nonpolyposis colon cancer. Cancer Genetics Studies Consortium.

OBJECTIVE: To provide recommendations for cancer surveillance and risk reduction for individuals carrying mutations associated with hereditary nonpolyposis colon cancer (HNPCC). PARTICIPANTS: A task force with expertise in medical genetics, oncology, primary care, gastroenterology, and epidemiology convened by the Cancer Genetics Studies Consortium (CGSC), organized by the National Human Genome Research Institute (previously the National Center for Human Genome Research). EVIDENCE: Studies evaluating cancer risk, surveillance, and risk reduction in individuals genetically susceptible to colon cancer were identified using MEDLINE and bibliographies of articles thus identified. Indexing terms used were "genetics" in combination with "colon cancer," and "screening" in combination with "cancer family" and "HNPCC." For studies evaluating specific interventions, quality of evidence was assessed using criteria of the US Preventive Services Task Force. CONSENSUS PROCESS: The task force developed recommendations through discussions over a 14-month period. CONCLUSIONS: Efficacy of cancer surveillance or other measures to reduce risk in individuals who carry cancer-predisposing mutations is unknown. Based on observational studies, colonoscopy every 1 to 3 years starting at age 25 years is recommended for individuals known to have HNPCC-associated mutations. Endometrial cancer screening is also recommended, based on expert opinion concerning presumptive benefit. No recommendation is made for or against prophylactic surgery (ie, colectomy, hysterectomy); these surgeries are an option for mutation carriers, but evidence of benefit is lacking. It is recommended that individuals considering genetic testing be counseled regarding the unknown efficacy of measures to reduce risk and that care for individuals with cancer-predisposing mutations be provided whenever possible within the context of research protocols designed to evaluate clinical outcomes.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Comparison of phased-array and body coils for MR imaging of liver.

AIMS AND OBJECTIVES: To compare liver lesion conspicuity using torso phased-array (TPA) and body coils with two pulse sequences. METHODS: Sixty patients with 125 focal hepatic lesions underwent T2-weighted fast spin-echo (T2-FSE) and fast multiplanar inversion recovery (FMPIR) imaging with a standard body coil and with a TPA coil. The first 30 patients were scanned identically in both coils with four acquisitions; the second 30 were scanned with four acquisitions in the body coil and two in the TPA coil. RESULTS: Liver-lesion contrast-to-noise (C/N) was significantly higher for the TPA coil both with four acquisitions (P< 0.001) and with two acquisitions (P < 0.002) using FMPIR, compared to with four acquisitions in the body coil. Liver-lesion C/N for T2-FSE was equivalent in both coils. Liver-lesion C/N was significantly higher (P<0.01) for FMPIR than T2-FSE both in the body coil and in the TPA coil. CONCLUSION: Liver-lesion C/N was significantly higher using the TPA coil rather than the body coil. Imaging time can be reduced by decreasing the number of acquisitions with the TPA coil.

Adult↗
PubMed1997

Couple childbearing desires, intentions, and births.

Using new panel data from the National Surveys of Families and Households, I investigate the effects of wives' and husbands' childbearing desires on their spouses' intentions, and the effects of spouses' desires and intentions on subsequent births. The results show clearly that husbands' desires and intentions influence couples' births, with approximately equal force to that of wives' desires and intentions. When couples disagreed about wanting a child, each partners' intentions were shifted toward not having a child; and disagreement in desires or intentions were reflected in birth rates that were lower than average. These patterns were generally not different for couples with more or less traditional gender roles or attitudes.

Adult↗
PubMed1995

Informed consent for genetic research on stored tissue samples.

OBJECTIVE: To develop recommendations for obtaining adequate informed consent in the future when gathering tissue samples that may be used for genetic studies and defining the circumstances under which it is necessary to obtain further consent if tissue samples already in hand are to be used for such research. PARTICIPANTS: Scientists, ethicists, lawyers, and consumers selected by the National Center for Human Genome Research and the Centers for Disease Control and Prevention to represent a wide array of opinions. EVIDENCE: Statutes, regulations, and cases and articles on law and ethics. CONSENSUS PROCESS: Initial workshop, followed by circulation of several drafts of this document with opportunities for comment by workshop participants and others as well as smaller meetings involving participants with widely differing views. CONCLUSION: Genetic research using stored tissue samples poses an array of benefits and risks to individuals, researchers, and society. As a result, the workshop participants conclude that (1) informed consent is required for all genetic research using linkable samples unless conditions for limitation or waiver are met; (2) informed consent is not required for genetic research using anonymous samples but may be considered if identifiers are to be removed from currently linkable samples; (3) institutional review boards could usefully review all protocols that propose to use samples for genetic research; and (4) further work regarding these issues is warranted.

Anonymous Testing↗
PubMed1995

Measuring fertility demand.

We propose a multidimensional conceptualization of fertility demand and evaluate potential measures of each dimension, using data from a telephone survey of Wisconsin residents age 18-34. Most of the measures met tests for interval-level measurement; all produced high estimates of test-retest reliability. We found support for only two dimensions of demand, intensity and certainty; potential measures of centrality had relatively low associations with any of the latent dimensions. Demand certainty improved prediction of fertility expectations beyond a trichotomous (yes, no, don't know) measure, but demand intensity did not. We found mixed evidence for the conceptualization of fertility demand as a single continuum on which desire to avoid pregnancy is the opposite of desire to have a child.

Adolescent↗
PubMed1994

Sequence homologies and linkage group conservation of the human and mouse Cenpc genes.

Using a previously identified human CENPC cDNA fragment, we have isolated cDNA clones corresponding to the complete mouse Cenpc coding sequence. Using these cDNAs as probes to genomic libraries, we have isolated genomic clones corresponding to the mouse and human genes and also to a mouse pseudogene. In situ hybridization mapping of these genes reveals that the human gene maps to 4q12-q13.3 and the mouse gene to 5E2-E5. These sites are in a region of linkage group conservation between the two species. Secondary sites are present in man on chromosome 12q21.2-q21.33 and in mouse on chromosome 2B. This mouse secondary site is a pseudogene on the basis of DNA sequence. These secondary sites are not syntenic in the two species.

Amino Acid Sequence↗
PubMed1994

Screening of snake venoms for neurotoxic and myotoxic effects using simple in vitro preparations from rodents and chicks.

Eight snake venoms designated by the WHO as International Reference Venoms, and one additional venom were assessed for neurotoxic and myotoxic effects in vitro using the chick biventer cervicis and the rat and mouse phrenic nerve-diaphragm preparations. The objective was to determine whether any of the preparations could be used to detect evidence of neurotoxic or myotoxic activity prior to a more detailed examination. Bungarus multicinctus venom at concentrations above 1 microgram ml-1 selectively blocked neuromuscular transmission, with no direct effect on muscle fibres. Naja naja kaouthia and Notechis scutatus venoms selectively blocked neuromuscular transmission at low concentrations, but at higher concentrations both venoms caused direct effects on skeletal muscle resulting in contractures, loss of tension following direct stimulation and a loss in sensitivity to elevated [K+]0. Vipera russelli (Thailand) venom also blocked neuromuscular transmission but it was less potent than the venoms of B. multicinctus, N. n. kaouthia and N. scutatus. It also caused contractures in the chick biventer cervicis muscle. The venoms of Echis carinatus (Iran and Mali), Crotalus atrox, Bothrops atrox asper and Trimeresurus flavoviridis had limited neuromuscular blocking activity, and most of these venoms blocked [K+]0 and cholinoceptor stimulation in the chick muscle. Although both chick and rodent muscles allowed the assessment of neurotoxic and myotoxic activity, the chick biventer cervicis was simpler and more robust in use than either of the rodent phrenic nerve-diaphragm preparations. We propose that the chick biventer cervicis muscle could be used as a standard preparation for the screening of snake venoms for neurotoxic and myotoxic effects, and that it may be possible to use this preparation as a means to check that antivenoms can neutralize neurotoxic and direct myotoxic actions of venoms.

Animals↗
PubMed1993

Comparison of crotoxin isoforms reveals that stability of the complex plays a major role in its pharmacological action.

Crotoxin from the venom of the South American rattlesnake Crotalus durissus terrificus is a potent neurotoxin consisting of a weakly toxic phospholipase-A2 subunit (CB) and a non-enzymic, non-toxic subunit (CA). Crotoxin complex (CACB) dissociates upon interaction with membranes: CB binds while CA does not. Moreover, CA enhances the toxicity of CB by preventing its non-specific adsorption. Several crotoxin isoforms have been identified. Multiple variants of each subunit give different crotoxin complexes that can be subdivided into two classes: those of high toxicity and low enzymic activity and those of moderate toxicity and a high phospholipase-A2 activity. In this study, we demonstrate that the more-toxic isoforms block neuromuscular transmission of chick biventer cervicis preparations more efficiently than weakly toxic isoforms. The less-toxic crotoxin complexes have the same Km and Vmax as CB alone. In contrast, the more-toxic isoforms are enzymically less active than CB. These differences correlate with the stability of the complexes: less-toxic isoforms are less stable (Kd = 25 nM) and dissociate rapidly (half-life about 1 min), whereas the more-toxic isoforms are more stable (Kd = 4.5 nM) and dissociate more slowly (half-life 10-20 min). The rate of interaction of crotoxin complexes with vesicles of negatively charged phospholipids paralleled the rate of dissociation of the complexes in the absence of vesicles. The differences of pharmacological and biochemical properties of crotoxin isoforms indicate that the stability of crotoxin complexes plays a major role in the synergistic action of crotoxin subunits: a stronger association between the two crotoxin subunits would account for their slower dissociation rate, a weaker enzymic activity, a slower interaction with phosphatidylglycerol vesicles, a faster blockade of neuromuscular transmission and a higher lethal potency.

Animals↗