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Biomedical subjects

J Loudon

Publications and source records attributed to J Loudon.

At least 19 recordsLinked to original sources

Critical roles of a cyclic AMP responsive element and an E-box in regulation of mouse renin gene expression.

Mouse As4.1 cells, obtained after transgene-targeted oncogenesis to induce neoplasia in renal renin expressing cells, express high levels of renin mRNA from their endogenous Ren-1(c) gene. We have previously identified a 242-base pair enhancer (coordinates -2866 to -2625 relative to the CAP site) upstream of the mouse Ren-1(c) gene. This enhancer, in combination with the proximal promoter (-117 to +6), activates transcription nearly 2 orders of magnitude in an orientation independent fashion. To further delimit sequences necessary for transcriptional activation, renin promoter-luciferase reporter gene constructs containing selected regions of the Ren-1(c) enhancer were analyzed after transfection into As4.1 cells. These results demonstrate that several regions are required for full enhancer activity. Sequences from -2699 to -2672, which are critical for the enhancer activity, contain a cyclic AMP responsive element (CRE) and an E-box. Electrophoretic mobility shift assays demonstrated that transcription factors CREB/CREM and USF1/USF2 in As4.1 cell nuclear extracts bind to oligonucleotides containing the Ren-1(c) CRE and E-box, respectively. These two elements are capable of synergistically activating transcription from the Ren-1(c) promoter. Moreover, mutation of either the CRE or E-box results in almost complete loss of enhancer activity, suggesting the critical roles these two elements play in regulating mouse Ren-1(c) gene expression. Although the Ren-1(c) gene contains a CRE, its expression is not induced by cAMP in As4.1 cells. This appears to reflect constitutive activation of protein kinase A in As4.1 cells since treatment with the protein kinase A inhibitor, H-89, caused a significant reduction in Ren-1(c) gene expression and this reduction is mediated through the CRE at -2699 to -2688.

Animals↗

The association between Viadent use and oral leukoplakia.

Recently, leukoplakia of the maxillary vestibule was described in patients with no traditional risk factors but who had used Viadent products. We designed a case-control study to evaluate the hypothesis that Viadent users were more likely to have lesions. One hundred and forty-eight cases and controls were identified through the Section of Oral and Maxillofacial Pathology. Cases and controls were administered a questionnaire about Viadent use and other known risks. Results of crude, stratified, and logistic regression analyses showed that use of Viadent products was a risk indicator for leukoplakia (adjusted OR = 9.7, 95% CI = 4.7-21.6), with a strong dose-response relation.

Alcohol Drinking↗

Methotrexate and early postoperative complications in patients with rheumatoid arthritis undergoing elective orthopaedic surgery.

OBJECTIVES: To determine whether continued methotrexate treatment increases the risk of postoperative infections or of surgical complications in patients with rheumatoid arthritis (RA) within one year of elective orthopaedic surgery. DESIGN: A prospective randomised study of postoperative infection or surgical complications occurring within one year of surgery in patients with RA who underwent elective orthopaedic surgery. SUBJECTS: 388 patients with RA who were to undergo elective orthopaedic surgery. Patients who were receiving methotrexate were randomly allocated to groups who either continued methotrexate (group A) or who discontinued methotrexate from two weeks before surgery until two weeks after surgery (group B). Their complication rates were compared with complications occurring in 228 patients with RA (group C) who were not receiving methotrexate and who also underwent elective orthopaedic surgery. MAIN OUTCOME MEASURES: Signs of postoperative infection were recorded, including rubor, discharge, systemic infection, and frequency of wound dehiscence as well as the incidence of any surgical complication requiring a secondary revision procedure that occurred within one year of surgery. The frequencies of flare up activity of RA at six weeks and six months after surgery were also recorded. A flare of rheumatoid disease was defined as an increase in joint pain in two or more joints notified by the patient as well as by an increase in articular index of at least 25% after surgery. RESULTS: Signs of infection or surgical complications occurred in two of 88 procedures in group A (2%), 11 of 72 procedures in group B (15%), and 24 of 228 (10.5%) procedures in group C. The surgical complication or infection frequency in group A was less than that in either group B (p<0.003) or group C (p=0.026). At six weeks after surgery there were no flares in group A, six flares in group B (8%), and six flares in group C (2.6%). Logistic regression analysis of the overall surgical complication rate in all the patients with RA studied showed that methotrexate, whether continued or discontinued before surgery, did not increase the early complication rate in the patients with RA who underwent elective orthopaedic surgery. Other drugs-penicillamine, indometacin, cyclosporin, hydroxychloroquine, chloroquine, and prednisolone-all did significantly increase the risk of infection or surgical complication after elective orthopaedic surgery. The risk of surgery was also increased in the presence of intercurrent chronic diseases-diabetes, hypertension, bronchiectasis, psoriasis, asthma, and ischaemic heart disease. CONCLUSION: Continuation of methotrexate treatment does not increase the risk of either infections or of surgical complications occurring in patients with RA within one year of elective orthopaedic surgery. Thus methotrexate treatment should not be stopped in patients whose disease is controlled by the drug before elective orthopaedic surgery.

Adult↗

Knee joint accessory motion following anterior cruciate ligament allograft reconstruction: a preliminary report.

Early in the postoperative period, changes in tibial translation have been noted in patient populations following anterior cruciate ligament reconstructive surgery. Deformation due to a lengthening of the ligament graft has been the most widely accepted reason for the change in tibial translation. Treatment techniques have not been proven successful in the abatement or reversal of this graft lengthening. The purpose of this study was to investigate the effect of functional bracing on tibial translation during the first year postoperatively in a group of patients with early changes in tibial translation. Three consecutive patients with early increases in KT-2000 manual maximum total drawer following bone-patellar tendon-bone allograft reconstruction were identified as subjects in the control group. Five consecutive anterior cruciate ligament bone-patellar tendon-bone allografts with early increases in KT-2000 manual maximum total drawer were identified as subjects in the treatment group. These patients were followed monthly during the first year postoperatively by manual maximum total drawer KT-2000 testing. Criteria for inclusion in the treatment and control groups included KT-2000 testing, with an increase in translation of greater than or equal to 2 mm when compared with the uninvolved knee during the first year postoperatively. The treatment group was required to wear a functional knee brace during all weight-bearing activities until KT-2000 displacement measures were stabilized for 3 consecutive months. Treatment with the functional brace resulted in a mean 2.3-mm decrease in tibial translation in the manual maximum total drawer KT-2000 when comparing the involved and uninvolved knee prebracing with posttreatment. All five subjects in the treatment group had a decrease in tibial translation. A Median Test comparing the control and treatment group's KT-2000 scores was significant at the p < .05 level. Patients who experience early increases in tibial translation with anterior cruciate ligament reconstructions may be assisted in a reduction of the displacement by the use of a functional brace.

Adolescent↗

Joint moments in minor limb length discrepancy: a pilot study.

A biomechanical analysis was performed to determine if a minor limb length discrepancy alters lower extremity joint mechanics significantly and in a manner that could contribute to the development of joint abnormalities. Ten healthy subjects with equal limb lengths were recruited. Gait analysis was performed for both left and right sides to determine the maximum moments at the hip, knee, and ankle joints. A minor limb length discrepancy was simulated by adding a shoe lift of 1.25 cm to the left leg. After a period of acclimation, the gait was reanalyzed. Differences for maximum joint moments at the hip, knee, and ankle before and after simulation were nonsignificant. An additional 10 healthy, asymptomatic patients with actual limb length discrepancies ranging from 1 cm to 2 cm were also recruited. Gait analysis for maximum joint moments before and after correction of the limb length discrepancy was performed. Side-to-side differences in joint moments before correction were nonsignificant. After correction of the limb length discrepancy, side-to-side joint moment differences were significantly increased (P = 0.02) and may suggest acute overcompensation to the presence of the corrective shoe lift. Consequently, this study did not find an association between minor limb length discrepancies and predictable changes in lower extremity joint kinetics that might potentially lead to joint abnormalities.

Adolescent↗

Synthesis and evaluation of a series of aryl[e]fused pyrazolo[4,3-c]pyridines with potential anxiolytic activity.

A series of pyrazolo[4,3-c]pyridines has been synthesized and evaluated as potential anxiolytic agents. Selected compounds from this series show a pharmacological profile of action different from that of diazepam. A number of the compounds possess higher affinity for central benzodiazepine receptors than diazepam, yet show less anticonvulsant activity and are less sedative. The structure-activity relationships of these potential anxiolytic agents are discussed.

Animals↗

An open multicentre study of the treatment of florid schizophrenia with remoxipride.

Remoxipride, a novel substituted benzamide, was given for 4 weeks to 18 florid schizophrenics in an open study. The mental state of the majority improved as measured by the Brief Psychiatric Rating Scale. Remoxipride itself did not appear to cause troublesome extrapyramidal effects. There were no significant adverse effects on the cardiovascular system and no significant abnormalities in laboratory tests. These results suggest that remoxipride has antipsychotic effects, and that this should be tested in controlled clinical trials.

Adolescent↗

Growth of Mycobacterium leprae in nude mice.

Athymic nude mice were introduced in our laboratories in 1982. In this paper results over one year period of nude mice inoculated with small numbers of M. leprae are described. In this study we showed that 1 X 10(4) M. leprae with low numbers of viable bacilli inoculated into hind foot pads of nude mice housed both in vinyl plastic isolators and "clean room" conditions had the ability to grow and reach remarkable levels. There was dissemination of the infection to other uninoculated foot pads by six months.

Animals↗

The effects of sterilisation: a comparison of sterilised women with the wives of vasectomised men.

In a follow-up study, women sterilised by tubal diathermy were compared with a matched group of wives of vasectomised men. Semi-structured interviews were given to a random sample drawn from a representative population. The couples were young with small families and did not have a high proportion of unplanned pregnancies or terminations. They had previously used contraception, mainly the pill or sheath. Most couples were entirely satisfied with the operation. Both groups showed an increase in pre-menstrual symptoms but there was only slight evidence that menstrual loss was affected by female sterilisation. The vasectomy couples had a higher frequency of sexual intercourse, few sexual problems and tended to have more satisfactory marriages. They had had more discussion of their decision to have the operation and the implications of counselling are considered.

Coitus↗

Two types of insomnia: too much waking or not enough sleep.

The stability of sleep was examined in two kinds of induced insomnia, namely after caffeine administration and after hypnotic drug withdrawal. The duration of each episode of any one sleep stage or any episode of intervening wakefulness plus drowsiness was determined. After caffeine there was an increase in longer episodes of intervening wakefulness plus drowsiness, but no significant change in the episode duration of any of the sleep stages. In the case of drug withdrawal there was no change in the episode duration of intervening wakefulness plus drowsiness, but there was a significant shortening of episode duration in sleep stages 2 and 3+4, with a similar trend for REM sleep episodes. Caffeine 'insomnia' thus seems characterized by increased stability of wakefulness, and hypnotic withdrawal 'insomnia' by decreased stability fo sleep. The type of analysis undertaken in this study could increase understanding of other types of insomnia.

Age Factors↗

Sanguinaria-related leukoplakia: epidemiologic and clinicopathologic features of a recently described entity.

An association between the use of Viadent toothpaste and/or mouthwash and the development of leukoplakia oral mucosal lesions has been described recently. Discontinuing the Viadent products may result in resolution of the leukoplakia, although frequently this is not the case. In order to corroborate the earlier study and to provide further insight regarding the clinical features of this process, a case-control study was conducted. A significant association was seen between the use of Viadent products and the development of oral leukoplakia. Furthermore, leukoplakias affecting sites other than the buccal vestibule also were associated with the use of these products.

Alkaloids↗

The nurse writer.

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Career Choice↗

Primary dapsone resistant leprosy in Nepal.

Mouse foot pad testing for primary dapsone resistant leprosy was performed in 15 patients. 13 were resistant (87%). Two patients below 10 years were living with lepromatous leprosy mothers, one male aged 21, was born in Kokana leprosarium and ten others gave no history of known contact of leprosy.

Adolescent↗