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Biomedical subjects

M Briggs

Publications and source records attributed to M Briggs.

At least 55 records · Page 3Linked to original sources
PubMed1996

PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene.

Increased activity of lipoprotein lipase (LPL) may explain the hypotriglyceridemic effects of fibrates, thiazolidinediones and fatty acids, which are known activators (and/or ligands) of the various peroxisome proliferator-activated receptors (PPARs). Treatment with compounds which activate preferentially PPARalpha, such as fenofibrate, induced LPL expression exclusively in rat liver. In contrast, the antidiabetic thiazolidinedione BRL 49653, a high affinity ligand for PPARgamma, had no effect on liver, but induced LPL expression in rat adipose tissue. In the hepatocyte cell line AML-12, fenofibric acid, but not BRL 49653, induced LPL mRNA, whereas in 3T3-L1 preadipocytes, the PPARgamma ligand induced LPL mRNA levels much quicker and to a higher extent than fenofibric acid. In both the in vivo and in vitro studies, inducibility by either PPARalpha or gamma activators, correlated with the tissue distribution of the respective PPARs: an adipocyte-restricted expression of PPARgamma, whereas PPARalpha was expressed predominantly in liver. A sequence element was identified in the human LPL promoter that mediates the functional responsiveness to fibrates and thiazolidinediones. Methylation interference and gel retardation assays demonstrated that a PPARalpha or gamma and the 9-cis retinoic acid receptor (RXR) heterodimers bind to this sequence -169 TGCCCTTTCCCCC -157. These data provide evidence that transcriptional activation of the LPL gene by fibrates and thiazolidinediones is mediated by PPAR-RXR heterodimers and contributes significantly to their hypotriglyceridemic effects in vivo. Whereas thiazolidinediones predominantly affect adipocyte LPL production through activation of PPARgamma, fibrates exert their effects mainly in the liver via activation of PPARalpha.

3T3 Cells↗
PubMed1996

Clinical and neuropathological correlates of apolipoprotein E genotype in Alzheimer's disease. Window on molecular epidemiology.

Inheritance of the apolipoprotein E (apo E) epsilon 4 allele has recently been found to be associated with Alzheimer's disease. We have studied the clinical and neuropathological correlates of apolipoprotein E genotype in a large group of Alzheimer's patients. The primary influence on clinical presentation is a shift towards earlier age of onset in individuals who have the apo E epsilon 4 gene: no change in clinical course was observed. In neuropathological studies, we find that the major influence of apo E epsilon 4 is on increased A beta deposition. These results led to a model of the biological interaction between the apo E protein and Alzheimer's disease.

Age of Onset↗
PubMed1996

Apolipoprotein E and cognitive change in an elderly population.

The apolipoprotein E (apoE) epsilon 4 allele is overrepresented, and the apoE epsilon 2 allele underrepresented, in Alzheimer's disease. To assess the risk of cognitive impairment in individuals with these genotypes in the general population, we studied a population-based sample of 1,899 individuals 65 years and older as a follow-up to the Iowa 65+ Rural Health Study. Multiple regression and logistic regression analyses demonstrated significant effects of apoE epsilon 4 and apoE epsilon 2 in predicting performance on a delayed recall task over a 4- to 7-year period. The magnitude of this effect was, however, fairly modest, with odds ratios for developing impairment of approximately 1.37 (95% confidence interval: 1.007, 1.850; p = 0.045) for apoE epsilon 4 and 0.53 (95% confidence interval: 0.368, 0.777; p = 0.001) for apoE epsilon 2. These effects were more pronounced in women than men. Importantly, 85% of elderly apoE E4/4 individuals (average age, 81) scored in the unimpaired range on a screening mental status test. Thus, many individuals reach old age without cognitive impair- ment despite inheritance of one or two apoE epsilon 4 alleles. This suggests that apoE genotyping will have limited utility as a diagnostic or prognostic indicator of cognitive decline in individuals.

Aged↗
PubMed1996

Hepatitis B nucleotide sequence analysis: linking an outbreak of acute hepatitis B to contamination of a cryopreservation tank.

An epidemiological investigation indicated that six patients treated in a haematology unit who developed acute hepatitis B may have been infected as a result of contamination of a liquid nitrogen bone marrow storage tank. The clinical details are described elsewhere (Tedder et al., 1995); we describe the virological methods used to support the findings. HBV DNA was amplified from sera using a nested PCR with primers for the surface gene, and a region encompassing precore, the 3' end of X, and the 5' end of core. HBV DNA was also extracted from the frozen detritus in the liquid nitrogen storage tank. After equilibration, the aqueous material was filtered, co-precipitated with albumin and polyethylene glycol and the HBV DNA extracted by phenol-chloroform and ethanol precipitation. Direct nucleotide sequence analysis indicated that four patients were infected with HBsAg subtype adw viruses which carried novel amino acid substitutions at codons 145 and 146 of the X gene. HBV DNA extracted from the storage tank detritus contained identical sequences. The samples from two other patients, subtype ayw, did not contain the novel sequence changes in X and had other sequence differences. These findings linked conclusively the four patients as a cluster and the rescue of HBV-DNA sequences from the contaminated storage tank by the method described confirmed this as the common source of infection. Two other HBsAg-positive patients were excluded from the cluster by sequence analysis. Demonstration of infection by this route has implications for the safe storage of bone marrow and other related biological materials.

Acute Disease↗
PubMed1996

Regulation of ob gene expression in rodents and humans.

The discovery of the obese gene in the mouse and its conserved homologue in humans has led to important discoveries in energy metabolism. One of the chief findings was the fact that the expression of the leptin gene was regulated and that it, in turn, could regulate metabolism and behavior. Much of the literature has focused on the physiological role of leptin in driving processes as diverse as reproduction, starvation defence, feeding behavior or body weight, all dependent on expression levels of the ob gene. Here, we will describe our work, in which we have begun to elucidate the regulatory processes controlling obese gene expression.

Animals↗
PubMed1996

Vertical orbital dystopia.

Many pathologic processes may lead to vertical orbital dystopia. We reviewed 47 consecutive cases seen over a 13-year period. Twenty-nine patients underwent eye leveling procedures to improve cosmesis, 2 of these by camouflage procedures and 27 by orbital translocation. Ten patients had 16 secondary operations. There was one death, serious complications occurred in 3 patients, and nuisance complications occurred in 20 others. Seven patients developed diplopia postoperatively, and in 6 patients it was troublesome. In these, it resolved fully in 2 patients, improved to be of no consequence in 2, and in the remaining 2 troublesome symptoms persisted requiring inferior oblique muscle recession in 1. Binocular vision was never restored when not present preoperatively, and in 3 patients temporary loss occurred. There was an overall modest but significant improvement in appearance after surgery. It is concluded that vertical orbital translocation is rewarding and worthwhile.

Abnormalities, Multiple↗
PubMed1996

A newly identified polymorphism in the apolipoprotein E enhancer gene region is associated with Alzheimer's disease and strongly with the epsilon 4 allele.

Apolipoprotein E allele 4 (apoE epsilon 4) is a major risk factor for late-onset AD. Inheritance of this allele is associated with an earlier age of onset of dementia in individuals with AD. It is unknown whether other polymorphisms in the apoE gene may influence the effect of apoE epsilon 4 on AD. We screened portions of the promoter enhancer element and of the apoE receptor binding domain for other polymorphisms that could affect risk of AD. In particular, a C/G polymorphism at position +113 of the apoE mRNA in the apoE intron 1 enhancer element (IE1) has been recently identified. We found no other polymorphisms. We studied the relationship of the two alleles of the IE1 polymorphism with AD and found an apparent association between IE1 G and AD (n = 94; p = 0.0515). However, the IE1 G allele is also closely associated with apoE epsilon 4 (p < 0.0001). When the presence of apoE epsilon 4 is covaried, the association between the IE1 G allele and AD is no longer statistically significant (odds ratio = 1.29, 95% confidence interval: 0.44, 3.78). In contrast, epsilon 4 is still highly associated with AD when IE1 G is controlled for (odds ratio = 5.91, 95% confidence interval: 3.29, 10.63). Furthermore, there is no significant association between the age of onset of dementia and the inheritance of the G allele. We believe that the apparent association between IE1 G and AD is a consequence of the association between the epsilon 4 and IE1 G alleles.

Adult↗
PubMed1996

Surgical wound pain: a trial of two treatments.

In order to compare postoperative incisional pain intensity, a prospective randomised controlled trial was conducted with two patient groups: a treatment group (treated with a film dressing left intact until suture removal) and a control group (treated with the existing wound-care protocol of a dry dressing removed after 48 hours). Patient-controlled analgesia consumption and infection rates in the two groups were also compared. A sample of 30 patients undergoing total abdominal hysterectomy was selected. Incisional wound pain, measured using a visual analogue scale (at rest, on movement and a 24-hour average) and the McGill Pain Questionnaire were recorded daily until discharge (four days). The pain scores were not significantly different between the groups on Days 1 or 2 postoperatively. However, on Day 3 (when the wounds in the dry dressing group were exposed), there was a statistically significant difference in 24-hour average pain. Those whose wounds were covered with the film dressing experienced less pain and requested fewer non-steroidal anti-inflammatory drugs on Day 3. Maintaining a cover over a surgical wound until suture removal appears to promote pain relief when compared to exposing wounds to the air. A film dressing was useful in this respect as it allowed inspection of the wound without removing the dressing.

Adult↗
PubMed1996

Documenting wound management.

An audit of new wound management guidelines was conducted in October 1993 at St James's University Hospital, Leeds. Five patients with wounds (including pressure sores, cavity wounds and leg ulcers) were randomly sampled in each ward. Where the number of patients with wounds in a ward was five or less, all patients were recruited. An audit questionnaire based on an agreed standard was completed for all wounds. The areas included in the audit were all wards in general surgery, orthopaedics, plastic surgery, gynaecology, intensive care, elderly care and medicine. A sample of 120 patients with 152 wounds was obtained, comprising pressure sores, leg ulcers and infected wounds. A new wound assessment form was used in 89.5% of wounds audited (136/152), and only one of these patients did not have a designated care plan. The audit process raised awareness of the issues involved. The process of reviewing documentation with the wound-care link nurse identified areas for further improvement. The guidelines and wound-care forms are now in widespread use.

Humans↗
PubMed1996

The principles of aseptic technique in wound care.

Research evidence on asepsis is patchy, ambivalent and cannot always be generalised. There is no substitute for assessment of the individual circumstances before each procedure. Handwashing is vital, well researched and uncontroversial.

Asepsis↗
PubMed1995

Investigation of hepatitis B virus transmission in a health care setting: application of direct sequence analysis.

An epidemiologically linked cluster of hepatitis B virus (HBV) infections was investigated using HBV DNA amplification by a nested polymerase chain reaction with primers complementary to the region around the immunodominant a determinant of the surface gene, part of the X and core genes, and precore region and direct nucleotide sequence analysis. The cluster, in which 2 persons died of fulminant hepatitis, comprised 1 blood donor, 2 patients, and 2 health care workers. The Kimura two-parameter method was used to compare variance among the cluster with that in the control samples, which were collected from 7 patients infected with the same HBV subtype. Significantly less variation occurred within the cluster than in the control group (unpaired t test, P < .05). In an unrooted phylogenetic tree analysis, the 5 study samples formed a cluster distinct from the controls. This direct molecular approach of analyzing conserved regions of the HBV genome differentiated between viruses involved in HBV transmission events.

Aged↗
PubMed1994

Fronto-orbital re-operation in craniosynostosis.

The need for fronto-orbital re-advancement is reported from all cases of craniosynostosis operated on in the Birmingham and Oxford Craniofacial Units since 1979. Analysis of the 219 cases demonstrates a significantly higher re-operation rate in cases of syndromal craniofacial dysostosis or unilateral coronal synostosis initially operated on below the age of 6 months. Mild bicoronal, sagittal and metopic synostotic cases, however, did uniformly well with the timing of initial surgery having little influence on the re-operation rates.

Age Factors↗
PubMed1994

Examining equipment for wound care: the use of forceps and cotton wool in dressing packs.

Wound care experts have, over recent years, questioned the routine use of forceps and cotton wool balls in packs used for cleansing and dressing wounds. Despite relevant research supporting this view, these items still appear in wound care packs in some hospitals and the basis for this practice, at times, does not seem to have been questioned. A project to explore the effect of introducing a new pack (substituting gloves and non-woven gauze for cotton wool and forceps) was undertaken at St James's University Hospital in the summer of 1993. Nurses' opinions regarding satisfaction with the new pack were explored along with whether they would prefer to use forceps. Results showed that the majority of nurses were satisfied with the new packs and found them an appropriate, acceptable alternative. The Accident and Emergency findings are reported with a discussion of the implications for practice.

Attitude of Health Personnel↗
PubMed1994

Minor head injury: pathophysiological or iatrogenic sequelae?

This study addresses the possibility that cognitive sequelae--albeit of a transient or minor character--can be associated with mild head injury. Twenty men (aged 16-30 years of age), whose post-traumatic amnesia did not exceed eight hours, were examined within 48 hours of their accident and again one month later. This unselected sample had no previous history of head injury. A control group of 20 men of similar socioeconomic background, was selected from medical wards (where they had been admitted for orthopaedic treatment or a minor operation). They were also retested one month after the first examination. Neuropsychological tests were selected to measure abilities often compromised after significant head injury, namely memory and attention. The experimental component consisted of the fractionation of a complex skill (paced addition) to probe for deficits at different stages of information processing: perception and input into storage; search for and retrieval of information from working memory; and paced and unpaced addition. In general, no significant difference was found between the experimental and control groups, with the possible exception of an initial decrement on two working memory tasks: probe digits and a keeping track task (where the subject has to keep in mind and update a number of variables at the same time). The keeping track paradigm, ostensibly of ecological relevance, may well be worth further exploration in memory research, and in studies of more severely head-injured patients. It is further suggested that the appropriate management and counselling of mildly head-injured patients may help to avert symptoms that are of psychological rather than pathophysiological origin.

Adolescent↗
PubMed1994

Reliability of diagnostic reporting for children aged 6-11 years: a test-retest study of the Diagnostic Interview Schedule for Children-Revised.

OBJECTIVE: This study examined the reliability of symptom reporting by community children of elementary school age and their parents on a version of the Diagnostic Interview Schedule for Children-Revised (DISC-R). METHOD: A sample of 109 children aged 6-11 years from an ongoing epidemiologic study were recruited for retest DISC-R interviews after completion of the study protocol. Retest interviews took place 7-18 days after the first interview and were conducted by interviewers who had no prior information about the subjects. Test-retest reliability for five common childhood psychiatric diagnoses was evaluated with the kappa statistic; the intraclass correlation coefficient was used to evaluate test-retest reliability of symptom scales. RESULTS: The reliability of the parents' reports on the DISC-R was good to excellent for attention deficit hyperactivity disorder and separation anxiety disorder; it was fair for overanxious disorder, oppositional defiant disorder, and conduct disorder. The children reported many fewer symptoms than the parents except for separation anxiety disorder; reliability was fair for separation anxiety disorder and poor for attention deficit hyperactivity disorder. The children were particularly unreliable in reporting about time factors, such as duration and onset of symptoms. When symptoms were considered without duration and onset, children's reports reached fair reliability for separation anxiety disorder, overanxious disorder, and attention deficit hyperactivity disorder but remained poor for oppositional defiant disorder. CONCLUSIONS: The results suggest that highly structured diagnostic interviews such as the DISC-R may not be appropriate for use with younger children of elementary school age in community-based studies.

Adolescent↗
PubMed1994

Thecal repair in post-surgical pseudomeningocoele.

A postsurgical pseudomeningocoele (PSPM) forms when cerebrospinal fluid extravasates through a dura-arachnoidal tear and becomes encysted within the wound. Patients may become symptomatic with wound swelling, headache and radiculopathy. A uniform method of repairing PSPMs is described which includes separation of the dura from the arachnoid, dural repair under operating microscope control, and the use of overlapped local flaps to reinforce the dura and obliterate the PSPM sac. Four recent cases are presented which were successfully treated using this method.

Adult↗