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Biomedical subjects

M Price

Publications and source records attributed to M Price.

At least 37 records · Page 2Linked to original sources

Impact of a multidisciplinary day program on disease and healthcare costs in children and adolescents with severe asthma: a two-year follow-up study.

For patients whose asthma remains in poor control necessitating high utilization of medical services, a referral to a specialized "center of excellence" is often considered. A decade ago, we evaluated our pediatric asthma program of long-term hospitalization (median stay of 75 days) and found significant decreases in subjects' medical utilization following this intervention. In an effort to contain treatment costs, the former program was markedly altered to one of abbreviated stay with emphasis on family management of asthma. The purpose of the present study was to determine the outcome of children treated in the revised program with regard to disease severity, quality of life, and subsequent utilization of medical resources. Children with severe asthma who were admitted to the program and fulfilled study criteria were consecutively enrolled. Data was obtained concerning disease characteristics, treatment, and quality of life at admission, and at 1 and 2 years following discharge. Medical records for the year prior to program admission and for the 2 years following discharge were coded for medical care encounters. Ninety-eight children, aged 9 months to 18 years (mean age, 10.9 years), were enrolled. They participated in the program for a mean of 15.6 ( +/- 8 SD), median of 15.0, and range of 2-51 treatment days. The group showed significant improvement (P < 0.0001) from admission to 1- and 2-year follow-up in median corticosteroid use, asthma functional severity, perceived competence in asthma management, and quality of life for both caregiver and child. Medical record data showed significant improvement (P < 0.0001) at both 1- and 2-year follow-up in median number of corticosteroid bursts, emergency department visits, hospital days, and overall utilization of medical care encounters. A median total medical encounter cost/patient of $16,250 ($6,972-$25,714 interquartile range (IQR)) for the year prior to program participation was reduced to $1,902 ($505-$6,524 IQR) at 1-year and $690 ($185-$3,550 IQR) at 2- year follow-up (P < 0.0001). We conclude that multidisciplinary care in a short-term, outpatient, day treatment program can significantly contribute to improvement in asthma severity, quality of life, and reduction in healthcare costs.

Adolescent↗

A prospective, randomized comparison of the use versus non-use of topical corticosteroids after laser in situ keratomileusis.

OBJECTIVE: To evaluate the benefit and safety of topical corticosteroids after laser in situ keratomileusis (LASIK). DESIGN: Prospective, randomized, double-masked clinical trial. PARTICIPANTS: A consecutive series of 1747 eyes in 897 patients desiring surgical correction of myopia from plano to -16 diopters (D) with up to 6 D of astigmatism. INTERVENTION: Patients were randomly assigned to topical corticosteroids or artificial tears. MAIN OUTCOME MEASURES: The primary outcome measure was stability of refraction. Secondary outcome measures were differences in best-corrected visual acuity, decrease in spherical refractive myopia, improvement in uncorrected visual acuity, predictability of achieved corrections versus planned corrections, evaluation of postoperative haze, preservation of best-corrected visual acuity, intraocular pressure, and incidence of complications and adverse events. RESULTS: No difference was found between the groups for refractive accuracy, best-corrected or uncorrected visual acuity, or safety. Topical corticosteroids were associated with a prolonged period of refractive regression in moderate to high myopes (-7.25 to -16.00 D) (P = 0.01). Increased haze was noted at the 1 week examination for eyes not receiving topical steroids (P = 0.008); however, in most cases this was clinically insignificant. Thirty-six eyes (2.1%) required supplemental topical corticosteroids unrelated to reoperation. Two eyes received these on the first postoperative day and 15 at the 1-week examination. CONCLUSIONS: Topical corticosteroids did not seem to play any beneficial role in routine postoperative treatment after LASIK, and they were associated with decreased stability of refraction in more highly myopic eyes. Eyes that require additional topical corticosteroids are easily identified at either the initial postoperative examinations or during the course of routine postoperative care.

Administration, Topical↗

Percutaneous core biopsy of the breast: correlates of anxiety.

RATIONALE AND OBJECTIVES: The authors performed this study to investigate the level of patient anxiety immediately preceding breast biopsy and examined potential clinical and demographic correlates of anxiety. MATERIALS AND METHODS: The authors evaluated 102 women who were referred to a radiology breast clinic to undergo breast biopsy. The women were assessed with a self-report of demographic and medical items and the State Trait Anxiety Inventory (STAI) immediately before their biopsy. The STAI also was administered at 1 and 5 days after biopsy. RESULTS: The participants' mean state anxiety T score as measured with the State Trait Anxiety Inventory was 71.1 (standard deviation, 7.2). Multiple regression analysis was performed to determine the correlates of state anxiety. The variables that showed the strongest correlation with state anxiety were trait anxiety, being concerned about the results of biopsy, education (less education was associated with more anxiety), age (an older age was associated with more anxiety), and number of relatives with breast cancer. Given the expected overlap (r = 0.55) between state and trait anxiety, a second regression analysis was performed that controlled for trait anxiety. The results of this analysis also identified age, being concerned about the results of the biopsy. and number of relatives with breast cancer as relevant correlates of state anxiety. CONCLUSION: Overall, the results give some indication of the characteristics of women likely to be most anxious before biopsy. Future research should assess the effectiveness of different strategies for addressing situational anxiety.

Adolescent↗

Patients' perspectives on the burden of recurrent genital herpes.

The purpose of this study was to quantify the impact of recurrent genital herpes (RGH) on health-related quality of life, healthcare resource and workplace productivity. This was a cross-sectional survey conducted in 5 countries (Australia, Denmark, Italy, The Netherlands and UK). Patients with a confirmed history of RGH completed the MOS 36-Item Short Form Health Survey (SF-36) and the Recurrent Genital Herpes Quality of Life questionnaire (RGHQoL). Questionnaires addressing frequency of access to healthcare services and workplace productivity were also completed and patients' medical history was obtained. Scores for 6 of the 8 domains of the SF-36 were significantly lower (P<0.001) i.e. worse, compared with scores for the normal population. The RGHQoL score was significantly lower in patients experiencing more frequent or more severe recurrences. Forty-five per cent of patients estimated that their work effectiveness was reduced by between 25% and 50% due to genital herpes symptoms.

Adolescent↗

MHC class II proteins contain a potential binding site for the verotoxin receptor glycolipid CD77.

Globotriaosyl ceramide or CD77 functions as a cell surface receptor for toxins of the Shiga toxin/verotoxin family and as a marker for germinal center stage B-cells. The B-cell protein CD19 and the interferon-alpha receptor possess verotoxin-like amino acid sequences in their extracellular domains, and CD77 has been shown to function in CD19-mediated adhesion and interferon-induced growth inhibition. The Burkitt's lymphoma cell line, Daudi, is similar to germinal center B-cells in their expression of CD77, CD19 and MHC class II molecules. Using the multiple sequence alignment program, ClustalW, we have identified a verotoxin-like amino acid sequence on the beta-chain of human and murine MHC class II molecules. Binding of CD77 at this site could modulate the peptide-binding properties of these MHC class II molecules. Using Western blot analysis of whole cell extracts, we found that CD77-positive Daudi cells have higher levels of HLA-D proteins than VT500 cells, a Daudi-derived CD77-deficient mutant cell line. In contrast, MHC class II-mediated adhesion and surface expression are similar in the two cell lines. Therefore, CD77 could play a functional or regulatory role in MHC class II-mediated functions specifically relating to antigen presentation by B-cells to T helper cells.

Amino Acid Sequence↗

Precisely positioned nucleosomes are not essential for c-fos gene regulation in vivo.

Chromatin architecture plays a decisive role in many aspects of transcription regulation. We have tested the role of specific chromatin structures in c-fos gene regulation, using a gene transfer system based on episomes derived from the Epstein-Barr virus (EBV). This system reproduces in several respects the chromatin structure and regulation of the chromosomal c-fos gene. Using this approach, we first demonstrate that the pausing of RNA polymerase II downstream of the transcriptional start site does not require precisely positioned nucleosomes. Indeed, changing the pattern of MNase hypersensitive sites along the transcribed sequence does not perturb RNA polymerase II pausing or the regulation of the c-fos gene. Next, we show that a putative nucleosome positioned between the SIE/SRE elements (-300) and the CRE/TATA elements (-36) is not necessary for activation by a variety of inducers. Accordingly, total or partial deletion of the putative nucleosome sequence does not disturb c-fos regulation while the two regulatory sites flanking the nucleosome sequence remain hypersensitive to MNase. As described in this paper, EBV episomes are useful vectors to critically examine the role of the chromatin structure in gene transcription for human cells.

Animals↗

Organization and conservation of the GART/SON/DONSON locus in mouse and human genomes.

The SON gene, which maps to human chromosome 21q22.1-q22.2, encodes a novel regulatory protein. Here we describe the organization of the Son locus in the mouse genome. The mouse Son gene spans a region of approximately 35 kb. The coding region is more than 8 kb in length and has been completely sequenced. The gene is organized into 11 coding exons and 1 noncoding 3'UTR exon, with over 70% of the coding region residing in one 5.7-kb exon. The gene contains at least one alternative exon, N/C exon 1, which can be used, by splicing, to generate a truncated form of the SON protein. Further investigation of the mouse Son locus has identified the genes directly flanking Son. The glycinamide ribonucleotide formyltransferase gene, Gart, is encoded 5' of Son in a head-to-head arrangement, with the start of both genes lying within 899 bp. Sequence comparison with the expressed sequence tagged database identified a novel gene within 65 bp of the 3' end of Son, which we have named Donson. In this unusually compact gene cluster, we have found overlap in the pattern of expression between Gart, Son, and Donson. However, at least two of these genes have very different functions. While GART is involved in purine biosynthesis, we find that SON shows the characteristics of "SR- type" proteins, which are involved in mRNA processing and gene expression.

Amino Acid Sequence↗

Cognitive function in UK community-dwelling African Caribbean and white elders: a pilot study.

In recent years there has been interest in risk of cognitive impairment and dementia in populations of African origin. Little is known about this risk in older African Caribbean residents in the UK. One difficulty is lack of consensus over an adequate cognitive test battery for this community. Forty-five African Caribbean and 45 age and gender matched white community residents were recruited by household enumeration of an inner London electoral ward. These participants were administered the MMSE during a screening interview. Where possible, this was followed up by tests from the CERAD and CAMCOG neuropsychological batteries, a medical examination, and a structured interview with an informant. Based on these data, a psychiatrist blind to ethnicity independently rated 86 of these participants (41 of the African Caribbeans, all 45 of the whites) as cognitively normal, cognitively impaired, or demented. Of 41 African Caribbeans, 18 (44%) were rated as cognitively normal, 9 (22%) were rated as cognitively impaired, and 14 (34%) were rated as demented. Of the 45 whites, 39 (87%) were rated as cognitively normal, 4 (9%) were rated as cognitively impaired, and 2 (4%) were rated as demented. African Caribbeans scored significantly lower than whites in most cognitive test scores, which was not accounted for by their lower educational and occupational attainment, or their higher frequency of cardiovascular risk factors. African Caribbean elders in the UK appear to be at high risk of cognitive impairment and dementia. However, the influence of potential confounding factors such as socio-economic position and ill-health, and the effect of cultural test bias, cannot be ruled out.

Aged↗

Behavioural measurement of postoperative pain after oral surgery.

The amount and type of postoperative analgesia prescribed depends on the clinician's judgement of the patient's need. Among other factors, this judgement is likely to be based on the patient's behaviour. The primary aim of this study was to investigate the validity of using behavioural measures to provide information about a patient's experience of pain during the early stages of recovery from oral surgery under general anaesthesia. Behavioural measures were not valid measures of acute postoperative pain, which suggests that while clinicians may build a better picture of a patient's experience of pain by including behavioural observation in their range of assessments, they should not rely on them when judging a patient's need for analgesia. The results also show differences between the sexes in their reaction to pain. Significantly more women than men showed signs of pain, despite little difference in self-rating pain scores.

Acetaminophen↗

Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat.

In mammals, exposure to antiandrogenic chemicals during sexual differentiation can produce malformations of the reproductive tract. Perinatal administration of AR antagonists like vinclozolin and procymidone or chemicals like di(2-ethylhexyl) phthalate (DEHP) that inhibit fetal testicular testosterone production demasculinize the males such that they display reduced anogenital distance (AGD), retained nipples, cleft phallus with hypospadias, undescended testes, a vaginal pouch, epididymal agenesis, and small to absent sex accessory glands as adults. In addition to DEHP, di-n-butyl (DBP) also has been shown to display antiandrogenic activity and induce malformations in male rats. In the current investigation, we examined several phthalate esters to determine if they altered sexual differentiation in an antiandrogenic manner. We hypothesized that the phthalate esters that altered testis function in the pubertal male rat would also alter testis function in the fetal male and produce malformations of androgen-dependent tissues. In this regard, we expected that benzyl butyl (BBP) and diethylhexyl (DEHP) phthalate would alter sexual differentiation, while dioctyl tere- (DOTP or DEHT), diethyl (DEP), and dimethyl (DMP) phthalate would not. We expected that the phthalate mixture diisononyl phthalate (DINP) would be weakly active due to the presence of some phthalates with a 6-7 ester group. DEHP, BBP, DINP, DEP, DMP, or DOTP were administered orally to the dam at 0.75 g/kg from gestational day (GD) 14 to postnatal day (PND) 3. None of the treatments induced overt maternal toxicity or reduced litter sizes. While only DEHP treatment reduced maternal weight gain during the entire dosing period by about 15 g, both DEHP and DINP reduced pregnancy weight gain to GD 21 by 24 g and 14 g, respectively. DEHP and BBP treatments reduced pup weight at birth (15%). Male (but not female) pups from the DEHP and BBP groups displayed shortened AGDs (about 30%) and reduced testis weights (about 35%). As infants, males in the DEHP, BBP, and DINP groups displayed femalelike areolas/nipples (87, 70, and 22% (p < 0.01), respectively, versus 0% in other groups). All three of the phthalate treatments that induced areolas also induced a significant incidence of reproductive malformations. The percentages of males with malformations were 82% (p < 0.0001) for DEHP, 84% (p < 0.0001) for BBP, and 7.7% (p < 0.04) in the DINP group. In summary, DEHP, BBP, and DINP all altered sexual differentiation, whereas DOTP, DEP, and DMP were ineffective at this dose. Whereas DEHP and BBP were of equivalent potency, DINP was about an order of magnitude less active.

Abnormalities, Drug-Induced↗

Reconstructive surgery in children after meningococcal purpura fulminans.

BACKGROUND/PURPOSE: Purpura fulminans (PF) is a serious, often life-threatening disease. As more children are surviving their disease, surgeons are presented with increasing numbers of multiple and complicated wounds as sequelae of PF. The purpose of this paper is to review the management of nine cases of PF, and present the reconstruction method in treating bilateral exposed elbow and knee joints. METHODS: All cases of pediatric patients with PF and treated by the division of plastic and reconstructive surgery between 1986 and 1998 were reviewed. RESULTS: Seven children (78%) had meningococcal PF, and one (11%) had PF after Haemophilus influenza septicemia. PF developed in one (11%) but with no growth in either blood or cerebrospinal fluid cultures. Five children (56%) required amputation procedures. Two children (22%) required knee disarticulation. Two patients (22%) had free myocutaneous flap transfers for bone coverage. One (11%) had PF involving the face. CONCLUSIONS: Meningococcal PF is a rare, often life-threatening disease generally of childhood. More children are surviving their diseases but with devastating sequelae. Successful reconstructive treatment outcome of these children requires a multidisciplinary team approach involving multiple specialties. The goal is to preserve function, maintain maximal length, and salvage limbs when possible. Flexibility and innovation are necessary in treating these multiple and complicated wounds.

Amputation, Surgical↗

Competence to stand trial: a neuropsychological inquiry.

How might the deconstruction of the legal theory of competence be related to modern neuropsychological models of cognition? To address this question, we examined retrospectively the relationship between clinical judgments of competence of defendants committed to a maximum security psychiatric facility and their neuropsychological test scores on measures of intelligence, memory, attention, academics, and executive function. In addition, based on both neuropsychological and legal theory, we examined whether subtypes of memory, namely episodic and semantic, and intelligence, specifically social intelligence, would have special relevance to these clinical judgements of competence. Results indicated that in relation to the defendants recommended as incompetent to stand trial (IST), defendants recommended as competent to stand trial (CST) scored significantly higher on summary indexes of psychometric intelligence, attention, and memory, especially verbal memory, but not significantly higher on tests of academics or executive function. Moreover, CST defendants scored significantly higher than did IST defendants on selective tests of episodic memory and social intelligence, but not on measures of semantic memory. Partial correlation also revealed a significant relationship between the likelihood of an IST recommendation and lower scores on tests of episodic memory and social intelligence, but not on measures of semantic memory. These findings illustrate the theoretical import of neuropsychological methods and concepts to the burgeoning nomological net known as competence.

Adolescent↗

Myocardial infarction and coronary artery involvement in giant cell arteritis.

PURPOSE: To describe the pathologic findings in an unusual case of giant cell arteritis that presented initially with visual loss and rapidly culminated in myocardial infarction. CASE REPORT: After the death of the patient, a complete autopsy was performed, including bilateral enucleation. All specimens, including a temporal artery biopsy completed before the patients death, were processed for routine paraffin histology and initially stained with hematoxylin and eosin. Elastic stains were subsequently used on specimens of temporal and coronary artery. The patient presented with loss of vision in the right eye. The clinical diagnosis was anterior ischemic optic neuropathy, secondary to temporal arteritis. The temporal artery biopsy was positive. Despite high-dose corticosteroid administration, the patient progressed to neurologic impairment, and subsequently to a fatal myocardial infarction. DISCUSSION: Previous reports of temporal arteritis with coronary involvement are summarized. Myocardial infarction may be a more common early complication of temporal arteritis than appreciated previously. This important complication can occur despite administration of high-dose corticosteroid therapy.

Aged↗

Tissue-specific chromatin structure at the hepatocyte growth factor/scatter factor gene promoter.

Hepatocyte growth factor/scatter factor (HGF/SF) is a recently characterised molecule with many remarkable functions. Its involvement in important processes such as cell proliferation, cell migration, morphogenesis and organ development implies that its activity should be tightly regulated. To understand the molecular mechanisms controlling HGF/SF transcription, we have analysed DNaseI hypersensitive sites (DHS) along rat and human HGF/SF genes in various tissues and cell types. We identified five DHS along the rat gene, two in the 5'-flanking region and three in the first intron. These sites are only found in rat tissues and rat cell lines, which express HGF/SF. The strongest hypersensitive site map to a region that corresponds to the promoter by start site analysis. A single tissue-specific DHS is present in human cell lines that express HGF/SF and corresponds to the promoter region. Our results suggest that chromatin accessibility plays a major role in the regulation of HGF/SF transcription regulation.

Animals↗

The use of remifentanil in general anaesthesia for caesarean section in a patient with mitral valve disease.

We report the use of remifentanil as part of a general anaesthetic technique for a patient with mixed mitral valve disease, asthma and pre-eclampsia presenting for an emergency Caesarean section. The use of remifentanil was associated with stable haemodynamic variables during general anaesthesia. No clinically significant respiratory depression was noted in the neonate.

Analgesics, Opioid↗