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Biomedical subjects

M Read

Publications and source records attributed to M Read.

At least 19 recordsLinked to original sources
PubMed2006

Management of miscarriage: expectant, medical, or surgical? Results of randomised controlled trial (miscarriage treatment (MIST) trial).

OBJECTIVE: To ascertain whether a clinically important difference exists in the incidence of gynaecological infection between surgical management and expectant or medical management of miscarriage. DESIGN: Randomised controlled trial comparing medical and expectant management with surgical management of first trimester miscarriage. SETTING: Early pregnancy assessment units of seven hospitals in the United Kingdom. PARTICIPANTS: Women of less than 13 weeks' gestation, with a diagnosis of early fetal demise or incomplete miscarriage. INTERVENTIONS: Expectant management (no specific intervention); medical management (vaginal dose of misoprostol preceded, for women with early fetal demise, by oral mifepristone 24-48 hours earlier); surgical management (surgical evacuation). MAIN OUTCOME MEASURES: Confirmed gynaecological infection at 14 days and eight weeks; need for unplanned admission or surgical intervention. RESULTS: 1200 women were recruited: 399 to expectant management, 398 to medical management, and 403 to surgical management. No differences were found in the incidence of confirmed infection within 14 days between the expectant group (3%) and the surgical group (3%) (risk difference 0.2%, 95% confidence interval - 2.2% to 2.7%) or between the medical group (2%) and the surgical group (0.7%, - 1.6% to 3.1%). Compared with the surgical group, the number of unplanned hospital admissions was significantly higher in both the expectant group (risk difference - 41%, - 47% to - 36%) and the medical group (- 10%, - 15% to - 6%). Similarly, when compared with the surgical group, the number of women who had an unplanned surgical curettage was significantly higher in the expectant group (risk difference - 39%, - 44% to - 34%) and the medical group (- 30%, - 35% to - 25%). CONCLUSIONS: The incidence of gynaecological infection after surgical, expectant, and medical management of first trimester miscarriage is low (2-3%), and no evidence exists of a difference by the method of management. However, significantly more unplanned admissions and unplanned surgical curettage occurred after expectant management and medical management than after surgical management. TRIAL REGISTRATION NATIONAL RESEARCH REGISTER: N0467011677/N0467073587.

Abortion, Spontaneous↗
PubMed2004

Cognitive therapy for schizophrenia: treatment and dissemination.

Although medication is the treatment of choice for schizophrenia, most patients continue to experience exhibit residual symptoms despite compliance. Recent studies suggest that cognitive behavioral therapy (CBT) is useful in the treatment of schizophrenia and other psychotic disorders [1]. Results of previous studies suggest that patients treated with CBT, in conjunction with medication, exhibit decreased frequency and severity of delusions, hallucinations and negative symptoms. Finally, CBT has been shown to increase medication compliance in patients with schizophrenia and bipolar disorder. Speaking of the outcome data on CBT, Weiden was recently quoted as saying, "if this were a patented drug trial, you would have heard about [these findings]" [2]. Despite the empirical evidence supporting the use of CBT in patients with schizophrenia, this treatment is relatively unknown to the psychiatric community. This article will review the mechanisms and findings associated with CBT and schizophrenia, and suggest future directions for dissemination in the psychiatric community.

Cognitive Behavioral Therapy↗
PubMed2002

Pharmacokinetics of recombinant factor IX after intravenous and subcutaneous administration in dogs and cynomolgus monkeys.

Hemophilia B therapy requires intravenous (IV) infusions of large volumes of factor IX due to the low concentration of factor IX in concentrates (approximately 100 IU/mL). High concentration recombinant factor IX (rFIX) could be a significant advance since it would reduce the large volumes necessary for IV dosing and allow for low-volume subcutaneous (SC) administration. To evaluate high concentration factor IX, we produced formulations with either 2,000 or 4,000 IU/mL and studied the SC bioavailability in beagle dogs, cynomolgus monkeys and hemophilia B dogs along with efficacy in hemophilia B dogs. Beagle dog SC bioavailability was 86.4% using a 2000 IU/mL formulation and 77.0% using a 4000 IU/mL formulation. Monkey bioavailability of a 4000 IU/mL formulation of rFIX was 34.8%. A single SC administration of 200 IU/kg (4000 IU/mL) of rFIX to hemophilia B dogs, produced factor IX clotting activity above 5% for 5 days with a bioavailability of 48.6%. High concentration SC rFIX has an acceptable pharmacokinetic profile in monkeys and dogs, and produces a sustained FIX activity in hemophilic dogs.

Animals↗
PubMed2001

The Eurasian heartland: a continental perspective on Y-chromosome diversity.

The nonrecombining portion of the human Y chromosome has proven to be a valuable tool for the study of population history. The maintenance of extended haplotypes characteristic of particular geographic regions, despite extensive admixture, allows complex demographic events to be deconstructed. In this study we report the frequencies of 23 Y-chromosome biallelic polymorphism haplotypes in 1,935 men from 49 Eurasian populations, with a particular focus on Central Asia. These haplotypes reveal traces of historical migrations, and provide an insight into the earliest patterns of settlement of anatomically modern humans on the Eurasian continent. Central Asia is revealed to be an important reservoir of genetic diversity, and the source of at least three major waves of migration leading into Europe, the Americas, and India. The genetic results are interpreted in the context of Eurasian linguistic patterns.

Adult↗
PubMed2001

Structure-based design of selective and potent G quadruplex-mediated telomerase inhibitors.

The telomerase enzyme is a potential therapeutic target in many human cancers. A series of potent inhibitors has been designed by computer modeling, which exploit the unique structural features of quadruplex DNA. These 3,6,9-trisubstituted acridine inhibitors are predicted to interact selectively with the human DNA quadruplex structure, as a means of specifically inhibiting the action of human telomerase in extending the length of single-stranded telomeric DNA. The anilino substituent at the 9-position of the acridine chromophore is predicted to lie in a third groove of the quadruplex. Calculated relative binding energies predict enhanced selectivity compared with earlier 3,6-disubstituted compounds, as a result of this substituent. The ranking order of energies is in accord with equilibrium binding constants for quadruplex measured by surface plasmon resonance techniques, which also show reduced duplex binding compared with the disubstituted compounds. The 3,6,9-trisubstututed acridines have potent in vitro inhibitory activity against human telomerase, with EC(50) values of up to 60 nM.

Acridines↗
PubMed2000

The effect of orthodontic referral guidelines: a randomised controlled trial.

OBJECTIVE: To develop and evaluate the effectiveness of referral guidelines for the referral of orthodontic patients to consultant and specialist practitioner orthodontists. DESIGN: Single centre randomised controlled trial with random allocation of referral guidelines for orthodontic treatment to general dental practitioners. SETTING: Hospital orthodontic departments and specialist orthodontic practices in Manchester and Stockport. SUBJECTS: General dental practitioners and the patients they referred for orthodontic treatment. MAIN OUTCOME MEASURE: Appropriateness of referral, defined as whether the patient was accepted for orthodontic treatment. RESULTS: The referral guidelines did not reduce the number of inappropriate referrals. CONCLUSIONS: Referral guidelines for orthodontic referrals did not influence the behaviour of the general dental practitioners. More research into the optimum methods of dissemination and implementation of referral guidelines for use in the general dental service is needed.

Adolescent↗
PubMed2000

Reported adoption of dietary fat and fiber recommendations among consumers.

OBJECTIVE: To identify constraints in adopting dietary fat and fiber recommendations. DESIGN: A questionnaire was mailed to a sample of the general population, a convenience sample of persons with heart disease and cancer in 11 states, and registered dietitians in 5 states. The survey included questions on demographic and attitudinal factors that were correlated with specific practices to reduce fat intake and increase fiber intake. SETTING: From the general population sample of 6,206 eligible respondents (return rate of 51.5%), those selected were respondents who indicated that they would adopt a dietary recommendation if it were good for them (n = 2,682). Subsamples from the general population were matched to 362 registered dietitians and 147 persons with cancer or heart disease on selected demographic variables. Factors associated with adoption of specific behaviors were identified. STATISTICAL ANALYSIS PERFORMED: Statistical analysis included chi 2, factor analysis, and analysis of variance. RESULTS: The majority of persons who said they would adopt a fat-reducing behavior if it were good for their health reported practicing that behavior often or usually. More than 60% reported consuming whole grains; however, only 15% reported eating fruits and vegetables frequently. Among the general population sample, those more likely to practice a behavior had the following characteristics: female, college educated, older than 60 years, white, higher income, no children younger than 18 years, perceived health status as excellent, and absence of chronic disease. Registered dietitians and those with chronic disease were also more likely to follow dietary fat and fiber recommendations. APPLICATIONS: Nutrition education messages that lead to increased consumption of dietary fiber need to be developed. Nutrition educators should provide strategies for consumers for increasing use of fruits and vegetables in all meals. Good taste and convenience are critical components. The food industry may assist by providing a wider array of convenience entrees or side dishes that feature produce and whole grains.

Adult↗
PubMed2000

The p21(WAF1/CIP1) promoter is methylated in Rat-1 cells: stable restoration of p53-dependent p21(WAF1/CIP1) expression after transfection of a genomic clone containing the p21(WAF1/CIP1) gene.

Rat-1 cells are used in many studies on transformation, cell cycle, and apoptosis. Whereas UV treatment of Rat-1 cells results in apoptosis, X-ray treatment does not induce either apoptosis or a cell cycle block. X-ray treatment of Rat-1 cells results in both an increase of p53 protein and expression of the p53-inducible gene MDM2 but not the protein or mRNA of the p53-inducible p21(WAF1/CIP1) gene, which in other cells plays an important role in p53-mediated cell cycle block. The lack of p21(WAF1/CIP1) expression appears to be the result of hypermethylation of the p21(WAF1/CIP1) promoter region, as p21(WAF1/CIP1) protein expression could be induced by growth of Rat-1 cells in the presence of 5-aza-2-deoxycytidine. Furthermore, sequence analysis of bisulfite-treated DNA demonstrated extensive methylation of cytosine residues in CpG dinucleotides in a CpG-rich island in the promoter region of the p21(WAF1/CIP1) gene. Stable X-ray-induced p53-dependent p21(WAF1/CIP1) expression and cell cycle block were restored to a Rat-1 clone after transfection with a P1 artificial chromosome (PAC) DNA clone containing a rat genomic copy of the p21(WAF1/CIP1) gene. The absence of expression of the p21(WAF1/CIP1) gene may contribute to the suitability of Rat-1 cells for transformation, cell cycle, and apoptosis studies.

5' Untranslated Regions↗
PubMed2000

Evaluation of zuclopenthixol acetate to decrease handling stress in wapiti.

Handling stress and capture myopathy are important consequences of intensively managing wildlife species. Over the last 15 yr, the use of long-acting neuroleptic (LAN) drugs in wildlife has increased, and these drugs have become a valuable tool for decreasing capture and handling stress in many species. At this time, reports on the use of these drugs in North American species are limited. The major objective of this study was to evaluate the use of the LAN, zuclopenthixol acetate (Clopixol-Acuphase), to decrease both quantifiable and subjective measurements of stress and activity in wild wapiti (Cervus elaphus, North American elk). This blinded, randomized study took place in February 1999 in Manitoba (Canada) and involved 11 animals receiving the drug and 12 animals acting as controls. At 24 hr after drug administration, there were measurable and significant decreases in the stress and activity of treated animals versus controls during handling. Treated animals had significantly lower mean body temperatures (39.0 versus 40.6 C), less hemoconcentration (mean packed cell volume 0.42 versus 0.49, mean hemoglobin 159.09 versus 181.75 g/L, mean total protein 65.0 versus 70.25 g/L), lower mean serum cortisol (97.91 versus 139.50 mmol/L), lower mean blood lactate (3.39 versus 5.98 mmol/L), and were less metabolically acidotic (mean pHv 7.45 versus 7.34, mean bicarbonate 29.36 versus 24.25 mmol/L, mean base excess 5.64 versus -0.83 mmol/L). Only control animals had evidence of muscle damage based on serum biochemistry (creatine phosphate values of two animals of 42,080 and 25,887 U/L). No animals developed clinical capture myopathy, and no animals died. Measurable effects of this drug were still apparent at 72 hr post-administration. The results of this study support the use of Clopixol-Acuphase in wapiti as a means to decrease handling stress and activity.

Animals↗
PubMed1998

Rational drug design approach for overcoming drug resistance: application to pyrimethamine resistance in malaria.

Pyrimethamine acts by selectively inhibiting malarial dihydrofolate reductase-thymidylate synthase (DHFR-TS). Resistance in the most important human parasite, Plasmodium falciparum, initially results from an S108N mutation in the DHFR domain, with additional mutation (most commonly C59R or N51I or both) imparting much greater resistance. From a homology model of the 3-D structure of DHFR-TS, rational drug design techniques have been used to design and subsequently synthesize inhibitors able to overcome malarial pyrimethamine resistance. Compared to pyrimethamine (Ki 1.5 nM) with purified recombinant DHFR fromP. falciparum, the Ki value of the m-methoxy analogue of pyrimethamine was 1.07 nM, but against the DHFR bearing the double mutation (C59R + S108N), the Ki values for pyrimethamine and the m-methoxy analogue were 71.7 and 14.0 nM, respectively. The m-chloro analogue of pyrimethamine was a stronger inhibitor of both wild-type DHFR (with Ki 0.30 nM) and the doubly mutant (C59R +S108N) purified enzyme (with Ki 2.40 nM). Growth of parasite cultures of P. falciparum in vitro was also strongly inhibited by these compounds with 50% inhibition of growth occurring at 3.7 microM for the m-methoxy and 0.6 microM for the m-chloro compounds with the K1 parasite line bearing the double mutation (S108N + C59R), compared to 10.2 microM for pyrimethamine. These inhibitors were also found in preliminary studies to retain antimalarial activity in vivo in P. berghei-infected mice.

Animals↗
PubMed1998

Junior doctors. Night vision.

By establishing separate timetables for senior house officers and registrars, an obstetrics and gynaecology department has been able to reduce out-of-hours work while offering training relevant to the doctors' proposed careers. Following the establishment of a daily, open-access gynaecology clinic, extending the role of midwives has reduced the out-of-hours workload of junior doctors. Emergency admissions, a major feature of out-of-hours work, have fallen by a quarter.

Appointments and Schedules↗
PubMed1998

The management of coeliac disease.

One hundred children put on a gluten free diet because of suspected coeliac disease were followed for a mean period of 9.9 years. The diagnosis was eventually confirmed in 53. Under the age of two, 35 children showed subtotal villous atrophy in their initial biopsy but nine of these on subsequent gluten challenge and rebiopsy were found to tolerate gluten normally. Challenge and rebiopsy are also necessary for children over the age of two where the initial biopsy changes are less severe than subtotal villous atrophy. Such challenges can probably be carried out earlier than the recommended age of six given in the 1990 ESPGAN (European Society for Paediatric Gastroenterology and Nutrition) report with little risk of serious dental damage.

Biopsy↗
PubMed1997

p53 in polyoma virus transformed REF52 cells.

While cellular transformation by small DNA tumour viruses usually involves targeting the product of the p53 tumour suppressor gene by a virally encoded protein, none of the three polyoma virus (Py) specified T antigens have been observed to interact with p53. We show that primary mouse embryo fibroblasts and REF52 cells, which resemble primary cells in requiring co-operating oncogenes for transformation, cannot be transformed by the Py oncogene, middle T-antigen (PyMT), alone. These cells can be transformed by the complete Py early region, which encodes the Py large, middle and small T-antigens. We find that PyMT can transform rodent cells lacking a functional p53 protein (p53 null mouse embryo fibroblasts and DN-REF52 cells which contain a dominant negative p53). In Py transformed REF52 cells (Py-REF52) there is no significant accumulation of p53 protein, as opposed to SV40 transformed REF52 cells (SV-REF52) in which the amount of steady state p53 protein is elevated. However accumulation of p53 is observed following exposure of Py-REF52 cells to u.v. Treatment of Py-REF52 cells with X-rays results in a rapid increase in the levels of the p53-induced proteins p21/WAF1 and MDM2. In untransformed REF52 cells, X-irradiation causes p53 activation, which results in induction of both G1/S and G2/M blocks. In SV-REF52 and DN-REF52 cells, p53 abrogation results in the absence of both the G1/S and G2/M blocks. Only the absence of a G1/S block is observed in Py-REF52 cells exposed to X-irradiation. Together these results indicate that in contrast to most other DNA tumour viruses, Py does not appear to interfere with the DNA damage induced transactivation activities of the p53 protein but absence of a functional p53 protein can mediate transformation by the PyMT oncogene in the absence of other co-operating oncogenes. Possible modes of transformation by Py are discussed.

Animals↗
PubMed1997

Placental nitric oxide synthase activity and abnormal umbilical artery flow velocity waveforms.

OBJECTIVE: To assess the nitric oxide synthase activity in placentas from women with either normal or abnormal Doppler ultrasound umbilical artery flow velocity wave-forms who delivered by elective cesarean. METHODS: This prospective observational study involved 16 women admitted either for elective cesarean for standard obstetric indications (with normal umbilical artery Doppler waveform studies, n = 8) or with evidence of fetal or maternal complications of pregnancy (with abnormal umbilical artery Doppler studies, n = 8). Placental tissue was collected and frozen in liquid nitrogen immediately upon delivery. Following storage at -80C, nitric oxide synthase activity was analyzed by measuring the conversion of [3H]L-arginine to [3H]L-citrulline. RESULTS: Placentas from women with abnormal umbilical artery flow velocity waveforms showed significantly lower mean nitric oxide synthase activity than did placentas from women with normal umbilical artery flow velocity wave-forms (Vmax = 11.3 pmol/minute/mg protein versus 22.6 pmol/minute/mg protein). CONCLUSION: There is a statistically significant reduction in nitric oxide synthase activity in placentas from pregnancies with abnormal umbilical artery flow velocity waveforms.

Adult↗
PubMed1997

Ovine fetal umbilical artery Doppler systolic diastolic ratios and nitric oxide synthase.

OBJECTIVE: To evaluate the effect of nitric oxide synthase activity inhibition on the fetal lamb umbilical artery flow velocity waveform. METHODS: Five pregnant Corriedale cross ewes were operated on at 125-130 days' gestation. Fetal and maternal vascular catheters were inserted along with a Doppler flow meter cuff on the fetal common umbilical artery. Each fetus received a 40-minute intravenous (i.v.) infusion of N omega-nitro-D-arginine as a control, and then after a recovery period of 1 hour, a 40-minute i.v. infusion of N omega-nitro-L-arginine, an inhibitor of nitric oxide synthase activity. Maternal and fetal heart rate, blood pressure, blood gases, and fetal umbilical artery flow velocity waveforms were recorded at basal time and after the 40-minute i.v. infusions. RESULTS: There were no differences in fetal or maternal heart rate, blood pressure, or blood gases with the infusion of the nitric oxide synthase inhibitor N omega-nitro-L-arginine. However, N omega-nitro-L-arginine caused a significant increase (41%) in the fetal umbilical artery flow velocity waveform systolic to diastolic ratio (S/D) above the baseline levels. CONCLUSIONS: Inhibition of nitric oxide synthase activity in the lamb fetoplacental circulation with N omega-nitro-L-arginine is associated with an increase in the umbilical artery S/D.

Animals↗