Drinking problems, the matching hypothesis and a conclusion revised.
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Alcohol Drinking↗
Biomedical subjects
C Taylor
Publications and source records attributed to C Taylor.
Imprinting and anticipation. Are they relevant to genetic studies of schizophrenia?
Among 29 multiply affected pedigrees, age of onset among parents and offspring was examined for evidence of both anticipation and genomic imprinting. The results do not suggest that either mechanism is operating in schizophrenia, but only very large effects can be confidently excluded.
Adult↗
A ratio estimation method for determining the prevalence of cocaine use.
This paper presents an approach to estimating the prevalence of cocaine use, based upon a new ratio estimation technique. This method can be applied to random samples of overlapping populations for which no sampling frames exist. When the ratio estimation method is applied to the two study samples (drawn from populations of people using cocaine and people using heroin) the ratio of cocaine users to heroin users (C/H) was 1.55, with a 95% confidence interval of +/- 0.48. Such estimates should be applied with caution. However, if used with reference to national estimates of about 75,000 heroin users, application of the present estimate suggests that there may be about 116,000 cocaine users in the UK.
Adult↗
An isobolographic study of epidural clonidine and fentanyl after cesarean section.
Although the epidural administration of clonidine and fentanyl provides pain relief after surgery, the interaction between the two drugs has not been examined formally. This study used an isobolographic method to determine whether epidurally administered fentanyl and clonidine interact in an additive or synergistic manner. Ninety women with moderate to severe pain after elective cesarean section under epidural anesthesia were studied. Using a randomized, double-blind protocol, we assigned each patient to receive a single epidural injection of one of three doses of fentanyl, clonidine, or a fixed ratio combination. Pain relief, blood pressure (BP), heart rate (HR), and sedation were measured 15 min after injection. Each drug alone and in combination produced analgesia, as measured by pain relief scores, and reduced need for intravenous morphine. Although the effective dose producing analgesia in 50% of patients (ED50) for the mixture was only 52% of that predicted by an additive interaction, this did not differ significantly from additivity, likely due to large variability. Clonidine, alone or in combination with fentanyl, produced a minor reduction in BP, but did not affect HR or cause more sedation than fentanyl. Unlike studies in rodents, this clinical study did not demonstrate synergy between fentanyl and clonidine. This could reflect a true species difference or differences in methodologies used. Nonetheless, a reduced dose of fentanyl and clonidine can be combined for excellent analgesia.
Adult↗
Regression of breast cancer in four patients treated with tamoxifen: mammographic features.
OBJECTIVE: The purpose of this article is to illustrate the regression of breast cancer as seen on mammograms of women treated with tamoxifen. SUBJECTS AND METHODS: Four elderly patients 72-88 years old were diagnosed with breast cancer on the basis of mammographic features. No surgery was performed because of multiple medical problems. Tamoxifen was initiated and the patients were closely monitored with physical examination and mammography for a minimum of 2 years. RESULTS: In all cases, the features of malignancy seen on mammograms regressed. These results were documented by a decrease in the number of calcifications and in the size of spiculated masses. CONCLUSION: These results suggest that tamoxifen, or one of its metabolites, may alter the biochemical nature of breast cancer.
Aged↗
Acetaminophen ingestion in childhood--cost and relative risk of alternative referral strategies.
Acetaminophen is the pharmaceutical most frequently ingested by small children. Although past research has allowed the safe management of 90% of these ingestions at home, several thousand are still referred to emergency departments annually. With the goal of further reducing the number of unnecessary referrals, the risk/benefit considerations of alternate referral strategies were analyzed. In a retrospective poison center chart review study from 11 centers, the records of children between the ages 1 and 6 years who acutely ingested acetaminophen and were referred to a hospital for determination of serum acetaminophen concentration in 1986 and 1987 were identified using the database of the American Association of Poison Control Centers. Risk of hepatic injury was assigned on the basis of the Rumack-Matthew acetaminophen toxicity nomogram. The cohort was stratified in terms of the amount ingested and whether a pediatric or adult preparation was ingested. The direct cost of an evaluation was estimated from four centers. Sensitivity, specificity and direct cost of each risk identification strategy were calculated. Eight hundred sixty six of 2091 patients had a timed serum acetaminophen concentration recorded. Of these, three patients had results in the "probable risk" area of the nomogram. A referral reduction strategy which would refer only children who ingest 200 mg/kg or more of an adult preparation could eliminate 82% of referrals without missing any of these "probable risk" patients. Six other children were determined to have serum acetaminophen concentrations in an area of the nomogram labeled "possible risk". No referral reduction strategy explored identified all of these patients. The average charge for an emergency department evaluation in 1992 was $272.00. These data suggest that children less than six years of age who ingest pediatric acetaminophen products other than those from packages containing greater than 30 tablets or who ingest less than 200 mg/kg of an adult preparation may be safely managed at home without referral to a hospital. This strategy would result in significant cost savings and prevent unnecessary inconvenience to many patients and families.
Acetaminophen↗
Ministering to persons who face death. Practical guidance for care givers of persons making end-of-life treatment decisions.
It is time care givers learn how to minister effectively and sensitively to those making end-of-life treatment decisions. To do so, care givers need to be aware of the various meanings death and dying hold. Culture, religion, past experiences with death and dying, and current situations can all influence the way persons perceive death and dying. Sensitivity to who the patient and family are, to how they perceive the disease or illness, and to how this perception influences their ability to achieve their life goals is a critical care-giving skill. Sensitivity, however, need not result in value neutrality or tolerance. Care givers should not be mindless executors of patient or family demands. Care givers must learn to talk honestly with patients and families about how a particular disease is most likely to progress and about the types of decisions they are likely to need to make. And then care givers need to present options, remaining sensitive to the patients' beliefs, values, and interests. Persons who care for the dying will face three types of patients, who will require different types of responses. The three types are patients who welcome death, patients who accept death, and patients who fight death. For all types of patients, care givers must keep the care patient centered and responsive to patients' priorities; facilitate informed decision making; promote communication among the patient, family, and healthcare team; support autonomous decision making; mediate conflicts; and offer spiritual counseling.
Attitude to Death↗
Cosmology and change in Rwanda.
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Acquired Immunodeficiency Syndrome↗
Relationship between pruritus, transepidermal water loss, and biochemical markers of renal itch in haemodialysis patients.
The pathogenesis of pruritus in patients undergoing chronic haemodialysis is unknown. Dryness of the skin is common in uraemic patients, and a correlation between xerosis and pruritus has been reported. Transepidermal water loss (TEWL) is a measure of cutaneous barrier function and also reflects skin water content. In this study the transepidermal water loss was measured at four sites pre- and postdialysis in 20 subjects undergoing chronic haemodialysis and in 16 healthy controls. Patients were weighed before and after dialysis and blood was taken for measurement of urea, creatinine, calcium, magnesium, phosphate and haemoglobin. All patients had parathyroid hormone measured within 3 months of the assessment. There was no significant difference in TEWL between patients and controls, with control values in general being between pre- and postdialysis rates of TEWL, and no correlation between TEWL and the presence or absence of pruritus. There was no significant differences between the pruritic and non-pruritic patients for any of the biochemical markers measured. Finally there was no significant correlation between the percentage water loss and TEWL. These findings indicate that pruritus of chronic haemodialysis is not related to abnormalities of cutaneous permeability.
Adult↗
Family physicians' practices regarding Norplant.
BACKGROUND: Norplant is a method of long-term contraception that was introduced in the United States in January 1991. This study was designed to explore the extent to which family physicians currently offer and insert Norplant. METHODS: A cross-sectional descriptive survey design was used to elicit information from a random sample of family physicians belonging to the Ohio Academy of Family Physicians. RESULTS: Of the 242 (69% response rate) physicians responding to the questionnaire, 130 (54%) were offering Norplant to their patients and 60 (25%) were inserting the devices themselves. Physicians offering Norplant were more likely to be women, younger, board certified, and currently practicing obstetrics. The most common reasons cited by the 112 (46%) physicians who did not offer Norplant were concerns about side effects, lack of familiarity with the procedure, expense, and personal or religious reasons. Overall, 88% of physicians who offered Norplant to their patients were satisfied with the product's performance. CONCLUSIONS: Over one half of the physician participants were offering Norplant as a contraceptive option for their patients. Physicians who offered the system were satisfied with its performance, and many expressed the belief that this form of contraception might be particularly well suited to certain patient groups.
Adult↗
Non-dysplastic myelodysplasia?
Patients successfully treated for a malignancy with cytotoxic therapy have an increased risk of developing secondary myelodysplasia (MDS) and acute myeloid leukemia (AML). We report a patient in remission from Hodgkin's disease (HD) who remains hematologically normal 4 years after combination chemotherapy, but who has biological and genetic abnormalities characteristic of myelodysplasia. X-inactivation analysis using a 5' phosphoglycerate kinase (PGK) probe demonstrates polyclonal hematopoiesis, but cytogenetic analysis reveals a clonal population with a minority of metaphases having a 7q-deletion. NRAS mutations are not detectable 1 year after treatment, but are present in two separate clones (at codons 12 and 15) analyzed by single-stranded conformational polymorphism (SSCP), followed by cloning and sequencing 4 years after treatment. The presence of an activated NRAS with the same codon 12 mutation was independently confirmed by the nude mouse tumorigenicity assay. In vitro peripheral blood granulocyte-macrophage colony-forming units (CFU-GM) have changed from normal to undetectable levels while erythroid burst forming units (BFU-E) were significantly reduced on two occasions during the period of observation. These abnormalities are characteristic of MDS. Continued clinical follow-up will determine whether these evolving genetic and biological abnormalities pre-date the onset of clinical and morphological features of MDS.
Adult↗
Failure to find linkage between schizophrenia and genetic markers on chromosome 21.
We sought evidence for the involvement of mutations in the amyloid precursor protein gene (APP) in the pathogenesis of schizophrenia in two ways. First, linkage analysis was performed in a sample of 24 families multiply affected with schizophrenia. The genotypes were studied for GT12 (D21S210), a highly polymorphic microsatellite marker at the APP locus. Second, we used single strand conformation analysis (SSCA) to screen for mutations in exon 17 of APP in one affected member from each family and in a sample of 44 unrelated patients. In addition, we looked for linkage between schizophrenia and a series of highly polymorphic markers situated at approximately 20cM intervals along the long arm of chromosome 21. We were unable to find evidence for linkage to GT12 or the other markers studied. SSCA did not reveal any mutations in exon 17 of AP. We conclude that mutations within APP are an unlikely cause of schizophrenia. Moreover, this study provides no evidence for a major gene for schizophrenia on chromosome 21, and linkage can be excluded from much of this region under some genetic models.
Adult↗
Determination of the order of substrate addition to MspI DNA methyltransferase using a novel mechanism-based inhibitor.
The cloning and overexpression of the MspI DNA methyltransferase as a functional fusion with glutathione S-transferase is described. The fusion enzyme retains full biological activity and has been used to investigate the interaction of substrates and inhibitors with MspI DNA methyltransferase. The fusion enzyme has been purified to homogeneity in a single step on GSH-agarose and is free from contaminating exonuclease activity. The enzyme can be photolabelled with S-adenosyl-L-methionine and the level of incorporation of label is enhanced by the presence of a nonspecific DNA duplex. In the presence of a cognate oligodeoxynucleotide, no photolabelling was observed since methyl transfer occurs instead. The inclusion of a mechanism-based inhibitor of C-5 deoxycytidine DNA methylation (an oligodeoxynucleotide containing the base 2-pyrimidinone-1-beta-D-2'-deoxyribofuranoside in the position of the deoxycytidine to which methyl addition occurs), which is thought to form a covalent interaction with the reactive cysteine of such enzymes, led to an enhancement of S-adenosyl-L-methionine photolabelling which suggests that, in contrast with results obtained with EcoRII DNA methyltransferase [Som and Friedman (1991) J. Biol. Chem. 266, 2937-2945], methylcysteine is not the photolabelled product. The implications of the results obtained with this mechanism-based inhibitor are discussed with respect to other C-5-specific DNA methyltransferases. Gel-retardation assays in the presence of cognate oligodeoxynucleotides that contain the reactive pyrimidinone base in place of the deoxycytidine target base are described. These demonstrate that most probably a stable covalent bond is formed between the methyltransferase and this oligodeoxynucleotide. However, the alternative of extremely tight non-covalent binding cannot be rigorously excluded. Furthermore, the results from these experiments indicate that the reaction mechanism proceeds in a manner similar to that of HhaI DNA methyltransferase with sequence-specific DNA binding being followed by addition of S-adenosyl-L-methionine and concomitant isomerization of the ternary complex leading to methyl transfer. S-Adenosyl-L-homocysteine appears to inhibit the reaction pathway as a result of either competition with the methyl donor and potentiation of a high-affinity interaction between the enzyme and DNA in an abortive ternary complex or through an allosteric interaction.
Base Sequence↗
Effects of co-factor and deoxycytidine substituted oligonucleotides upon sequence-specific interactions between MspI DNA methyltransferase and DNA.
MspI methyltransferase (M.MspI) catalyses the transfer of a methyl group from S-adenosyl-L-methionine to the C-5 position of the outer deoxycytidine base in the DNA sequence 5'-CCGG-3'. Recombinant M.MspI when expressed and purified as a translational fusion with glutathione-S-transferase, shows all of the properties of the wild-type enzyme. We report the kinetic analysis of M.MspI binding to DNA, which suggests a two-stage methylation process, whose initial DNA binding rate is governed by the presence of a positively charged sulphonium centre on the cofactor. Results are also presented that indicate that M.MspI binds preferentially to hemi-methylated DNA and that full methylation of either deoxycytidine on both strands significantly impairs sequence-specific protein-DNA interactions. Furthermore, the importance of the 4-amino group of the inner deoxycytidine for sequence-specific protein-DNA interactions is demonstrated by substituting deoxycytidine with 2-pyrimidinone-1-beta-D-2-deoxyriboside. In addition, we detail the intrinsic structural elements of a cofactor, required to enhance the binding of M.MspI to its recognition sequence, by using S-adenosyl-L-methionine and a range of derivatives.
Base Sequence↗
Increasing patients' knowledge of secondary contraception.
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Condoms↗
Harmonic regression analysis of the effect of drug treatment on the diurnal rhythm of blood pressure and angina.
Harmonic regression is a method for analysis of diurnal rhythms which we apply to blood pressure and angina attack rate. We show that population amplitude and phase as previously defined are not the expected values of amplitude and phase in the population unless patients are in phase and that the estimates of these population parameters are the amplitude and phase of the mean measurements of the observation times. We show that the amplitude of the mean measurements underestimates the magnitude of the diurnal rhythm of individual patients due to significant differences among patients in the phase parameter. Thus, the mean of the individual-patient amplitudes and phases, rather than the amplitude and phase of the mean measurements, is necessary to describe the diurnal rhythm in the population and to assess the effect of drug treatment. Harmonic regression analysis yields specific hypotheses that relate directly to the consistency of drug effect over 24 hours.
Amlodipine↗
Immunopathology of reactivation of experimental ocular histoplasmosis.
We have established a non-human primate model of experimental ocular histoplasmosis. This model has been shown to result in chronic lesions that resemble typical 'histo spots' or choroidal scars but that contain infiltrates of lymphocytes for as long as 10 yr following intracarotid injection of live Histoplasma capsulatum. Using this model, we attempted to reactive these late choroidal lesions via intracarotid challenge with specific antigen (heat-killed H. capsulatum). No clinical changes suggestive of reactivation of these lesions were observed following this antigenic challenge. However, immunopathologic analysis of choroidal lesions at 1, 3 and 7 days after antigenic challenge revealed significant increases in both the numbers of inflammatory cells and the relative percentages of the helper/inducer lymphocyte and macrophage populations. Our results demonstrate that, following antigenic challenge, a cellular change, consistent with a type IV delayed hypersensitivity, can be observed in previously active, but clinically quiescent, histoplasmosis lesions. In light of the many parallels between our primate experimental model and human ocular histoplasmosis, our findings suggest that, in the human, significant immunopathologic activity may occur subclinically in the choroid of affected individuals. It is possible that repeated bouts of subclinical reactivation may induce or enhance chronic choroiditis and, over many years, ultimately produce slow progressive damage to the Bruch's membrane/retinal pigment epithelium complex, resulting in clinically 'active' macular disease and, in selected cases, subretinal neovascularization.
Animals↗
A linkage study of schizophrenia with DNA markers from the long arm of chromosome 11.
We report the results of a collaborative linkage study using 12 polymorphic markers (9 loci) from the long arm of chromosome 11, and 24 families multiply affected with schizophrenia and other closely related disorders. This region is of interest because several families have been reported in which balanced translocations involving 11q apparently co-segregate with psychotic illness. In addition, the dopamine D2 receptor, porphobilinogen deaminase, and tyrosinase genes map within the region studied and may be aetiologically involved in schizophrenia. We have primarily analysed genotypic data by the LOD score method using a range of single gene models. In order to minimize error due to mis-specification of genetic parameters we have analysed data from markers at candidate gene loci by the non-parametric extended sib-pair method in addition to the LOD score method. Our results suggest that most of the region can be excluded from containing a gene of major effect in the aetiology of this disease.
Alleles↗