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Biomedical subjects

J G Edwards

Publications and source records attributed to J G Edwards.

At least 55 records · Page 3Linked to original sources

Prescription-event monitoring of 10,401 patients treated with fluvoxamine.

Prescription-event monitoring (PEM) is one of two national systems of drug safety monitoring practised in Britain. The objective of this PEM study was to assess the safety of fluvoxamine and to monitor the occurrence of untoward and other events during treatment. A total of 10,401 patients treated with the drug in general practices throughout England were studied and data were analysed in the Drug Safety Research Unit, Southampton. The main outcome measures were the overall incidence of events per 1000 patients; the incidence during the first month of treatment; the mean incidence for months 2-6 of treatment; and the ratio of these rates as a signal that an event could be drug related. The most commonly reported category of events was neuropsychiatric while the most commonly reported individual events were nausea and vomiting. Fluvoxamine was shown to be a safe drug and no unexpected or previously undetected drug-related events were encountered. There was a relatively high incidence of gastro-intestinal symptoms, but other adverse reactions often encountered during treatment with tricyclic antidepressants were not frequently reported.

Adolescent↗

Fluoxetine, amitriptyline and the electroencephalogram.

Electroencephalograms recorded before and after 4 weeks treatment of depressed patients with fluoxetine or amitriptyline were assessed visually and by power spectrum analysis blind to patient, treatment and whether the recordings were carried out before or after treatment. No significant between-group differences in alpha, beta or theta activity were found on visual assessment. Power spectrum analysis revealed a significant decrease in the amount of beta activity at week 4. There was no EEG evidence of drowsiness or epileptiform activity in either of the treatment groups.

Adult↗

Shapes of cells spreading on fibronectin: measurement of the stellation of BHK21 cells induced by raising cyclic AMP, and of its reversal by serum and lysophosphatidic acid.

In common with many other animal cells in culture, BHK21, CHO and NIH-3T3 cells adopt bizarre stellate or arborized shapes when exposed, in the absence of serum, to agents which increase cytoplasmic cyclic AMP (cAMP). Dibutyryl cAMP, 3-isobutyl-1-methylxanthine, 5'-deoxy-5'-methylthioadenosine, cholera toxin and the invasive adenylate cyclase from Bordetella pertussis all induce similar shapes. Time lapse video recording of BHK21 cells spreading on fibronectin shows that stellate shapes are generated by outgrowth of neurite-like processes led by small fans of ruffling membrane. These structures stain strongly for F actin, and their outgrowth is completely inhibited by cytochalasin D. Thus if stellation is caused by microfilament depletion, this must be selective for subsets of microfilaments. We have quantified the shape changes of BHK21 cells using the parameter dispersion. They are prevented by low concentrations (1% by volume and below) of bovine sera. The inhibitory component of foetal bovine serum acts humorally, behaves as a macromolecule and is itself inhibited by suramin, but platelet-derived growth factor, insulin, vasopressin and bradykinin are inactive. The inhibitory activity of serum may be due to phospholipids, since it can be replaced by lysophosphatidic acid in the presence of serum albumin.

3T3 Cells↗

Soft-tissue surgery to alleviate orthodontic relapse.

This article has presented three soft-tissue surgical techniques that have been shown to alleviate the relapse of orthodontically treated teeth in three specific situations: (1) rotations (and possibly also labiolingual irregularities), (2) extraction site closures, and (3) maxillary midline diastemas. The anatomy and histophysiology of the periodontium have been discussed briefly as they pertain to the rationale for these surgical procedures. None of the techniques discussed, if performed as indicated, will be detrimental to the supporting periodontal tissues and all can easily become a routine part of the clinician's standard retention therapy.

Diastema↗

A repressor region in the human beta-myosin heavy chain gene that has a partial position dependency.

Expression of the human beta-myosin heavy chain (beta MHC) gene was studied by transient assay in culture and in situ by direct injection of plasmids into adult rat hearts. In this report we describe a unique repressor region located -326/-309 (5'-TTGGTGGTCGTGGTCAGT-3') of the human beta MHC gene that is conserved among the rat, rabbit, and human beta MHC genes. This sequence conferred repression onto heterologous promoters when the sequence was located 5' but not 3' to the promoters. This partial positional dependency suggests that the factor may act by limiting the binding of enhancers, located more proximally, to their DNA binding sites.

Animals↗

Characterization of a strong positive cis-acting element of the human beta-myosin heavy chain gene in fetal rat heart cells.

A strong positive element within the proximal promoter region of the human beta-myosin heavy chain (beta-MHC) gene that is required for high level expression in primary cultures of fetal rat heart cells was localized by transient assays and DNase I footprinting to positions- 277/-298. Using gel shift studies, this sequence was found to bind specifically at high affinity (Kd approximately 4 x 10(-9) M) to a transcriptional factor (beta F1) found in nuclear extracts from rabbit heart. Dimethyl sulfate interference studies suggested that beta F1 may bind as a dimer to two hexameric imperfect direct repeats containing the consensus sequence 5'-(C/G)-T-G-(T/A)-G-G-3'. Gel shift analyses suggested that beta F1 is related to the M-CAT factor, which is known to control muscle-specific expression of the cardiac troponin T gene. A clustered mutation of the region between the putative binding half-sites and within the "M-CAT"-like domain abolished beta-MHC promoter activity. The sequence of the positive element also contains binding motifs for several transcriptional factors that regulate viral and cellular genes, including AP4, AP5, TEF-1, and MyoD-like proteins. When multiple copies of the beta-MHC element were inserted downstream from the transcriptional initiation site of the thymidine kinase gene, it did not act as a classical enhancer, showing some dependence upon orientation.

Animals↗

Type IV collagen and laminin in Bruch's membrane and basal linear deposit in the human macula.

Tissue obtained from the macula in 10 human eyes (53-77 years) was used for an investigation into the extracellular matrices of the retinal pigment epithelium (RPE), Bruch's membrane, and the choriocapillaris. The ultrastructural distribution of type IV collagen and laminin was documented using immunogold labelling. Labelling for type IV collagen was strongly positive in all the specimens in the basement membranes of the choriocapillaris but not that of the RPE where labelling was either weak or absent. Laminin was localised to deposits of granular material in Bruch's membrane but was absent from the basement membrane of the RPE and the choriocapillaris. Basal linear deposit, observed in three cases, demonstrated labelling for laminin but not for type IV collagen. The series was too small for correlation of these morphological changes with age.

Aged↗

A counseling dilemma involving anencephaly, acrania and amniotic bands.

A suggested fetal anencephaly on routine office ultrasound examination resulted in a diagnosis of fetal acrania when targeted ultrasonography was performed by a consultant. Following pregnancy termination, examination of the abortus revealed partial cranial destruction secondary to an amniotic band. It is often difficult to distinguish between anencephaly, acrania, and amniotic band sequence prenatally, but postnatal differentiation is imperative for accurate risk assessment in genetic counseling.

Adult↗

Attitudes toward presymptomatic testing and prenatal diagnosis for adrenoleukodystrophy among affected families.

One hundred and thirty-six individuals with a family history of X-linked adrenoleukodystrophy (ALD) or adrenomyeloneuropathy (AMN) were given a questionnaire surveying their sociodemographic characteristics, knowledge of X-linked inheritance, and attitudes toward prenatal, presymptomatic, and carrier testing. Of the respondents, 68% indicated that they would use prenatal testing. Of these, 57.1% would terminate a pregnancy of a male fetus hemizygous for the ALD gene and 13.5% would reportedly choose to terminate a heterozygote female fetus. Presymptomatic testing would be used by 88.7% of respondents to test at-risk sons and carrier testing would reportedly be used by 95.4% of respondents to test their at-risk daughters. Respondents correctly answered an average of 61% of the questions testing understanding of X-linked inheritance. This indicates a strong interest in prenatal, presymptomatic, and carrier testing and a need for genetic counselors to provide information about these available tests and X-linked inheritance.

Adrenoleukodystrophy↗

Single-center comparison of results of 1000 prenatal diagnoses with chorionic villus sampling and 1000 diagnoses with amniocentesis.

Large multicenter studies have confirmed the safety and accuracy of chorionic villus sampling as a prenatal genetic diagnostic procedure, but there have been few single-center evaluations. We report our experience with 1000 consecutive chorionic villus sampling procedures compared with 1000 consecutive amniocentesis procedures during the same period. The procedures were performed by the same genetic counselors, sonographers, obstetricians, and laboratory personnel. Indications for referral, demographic characteristics of patients, numbers of attempts per patient, fetal loss rates, laboratory results, and evaluation of accuracy are included. Analysis of all data suggests that chorionic villus sampling is a safe and accurate alternative to amniocentesis in our community-based teaching hospital.

Adult↗

Clinical anxiety and its treatment.

Anxiety occurs as a normal phenomenon and as a symptom of numerous psychiatric and physical illnesses, while it is the dominant feature of generalised anxiety, panic and phobic disorders. The relationship between these and other disorders is not as straightforward as diagnostic classifications suggest, and this is at least in part due to previous research having been carried out on atypical cases referred to hospital rather than patients in the real world of general practice and the general community. There are particular difficulties in distinguishing anxiety disorders from depressive illnesses, somatisation disorder and some cases of substance abuse and dependence. There may also be difficulty in deciding to what extent anxiety is related to stress or to the underlying personality of the patient. There are many reasons for these difficulties, including limitations in our basic knowledge of anxiety, preconceived notions of the clinician and the difficulty that some patients have in describing their experiences. Numerous different psychological and pharmacological treatments have been used throughout history. They include various forms of psychotherapy, behaviour and cognitive therapies and anti-anxiety drugs. Many patients receive supportive psychotherapy, while more specialised techniques currently being investigated include exposure therapy and cognitive therapy. By far the most widely used drugs are the benzodiazepines, but because of concern over dependence increasing interest is being shown in the use of alternatives, including antidepressants, and in the development of new compounds which, it is hoped, will turn out to be free from the problem of dependence.

Anti-Anxiety Agents↗

Pregnancy termination because of chromosomal abnormalities: a study of 26,950 amniocenteses in the southeast.

A regional study was done to investigate the outcome of chromosomally abnormal pregnancies with respect to the parental decision to continue or to terminate the pregnancy. Fourteen medical centers in the southeastern United States contributed data on 26,950 amniocenteses. In 416 cases (1.54%), cytogenetic abnormalities were reported. Of 378 singleton pregnancies in which a cytogenetic abnormality was reported and for which information regarding pregnancy outcome was available, the decision to terminate the pregnancy was made in 276 (73.02%). When the chromosomal abnormality was autosomal in nature, 240 of the 293 pregnancies (81.91%) were terminated, as compared to 36 of the 85 pregnancies (42.35%) affected with a sex chromosomal abnormality. Pregnancies involving the most common autosomal trisomies (21, 18, and 13) were terminated at a rate of 92% to 95%. No significant difference in the rate of abnormality or in the rate of pregnancy termination existed between the 14 centers. Our findings reflect the largest series of amniocentesis results collected to date.

Abortion, Induced↗

Effect of haloperidol decanoate on the cardiovascular system.

Rapid speed electrocardiograms were recorded in 13 chronic schizophrenic patients before, and at regular intervals during a six-month trial of haloperidol decanoate. Measurements of conduction intervals in the EEG were carried out blind to patient and to assessment interval. No significant changes in heart rate; PR, QRS on QTc intervals; or T-wave height were found. Neither was there a significant change in the blood pressure. The findings confirm that haloperidol does not have clinically relevant cardiac effects when given in therapeutic doses to physically healthy individuals.

Adult↗