Surgical pearl: Repair of split or deformed ear lobe with a tongue depressor blade for stabilization during surgery.
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Biomedical subjects
Publications and source records attributed to C Smith.
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Recovery from depletion of the readily releasable pool of vesicles (RRP) in adrenal chromaffin cells was studied at differing basal [Ca2+]i or following protein kinase C (PKC) activation by phorbol esters. Following depletion, the pool size was estimated at varied times from cell capacitance jumps in response to paired depolarizations. The experimentally observed RRP recovery time course and steady-state size could be predicted from the measured [Ca2+]i signal assuming a Michaelis-Menten-type regulation of the vesicle supply by Ca2+. An elevated recruitment activity was observed at increased [Ca2+]i even when protein kinase C was blocked, but maximum effects could be obtained only after stimulation of PKC by phorbol esters or by prolonged elevations in [Ca2+]i. We suggest that, in chromaffin cells, elevated cytosolic Ca2+ modulates exocytotic plasticity via PKC-dependent and -independent pathways.
The aim of this work was to design strong transcriptional activators that can be used to regulate plant gene expression. The contribution of different components in a transcription factor and target gene system was assayed by measuring transcriptional activation. Each component was optimised to achieve maximal reporter gene expression in transient protoplast transformation assays. The DNA-binding domain of the yeast transcriptional activator GAL4 was studied in the context of fusion proteins with activation domains of the herpes simplex virus protein VP16 or the tomato Myb-like activator THM18. Multimerisation of the activation domain and insertion of a homopolymeric glutamine stretch was used to increase transcription factor potency. Evidence is presented that these modifications can result in even more active transcription factors when they are combined. Finally, it was demonstrated using competition experiments that transcription factors with acidic activation domains can mutually suppress their activation potentials when expressed at high levels.
The injection of market forces into the National Health Service (NHS) has led to nurse education being viewed as a commodity which educational institutions supply and NHS employers purchase. Conscious of the costs of paying for courses within this new consumer culture, NHS trusts and other health service employers are increasingly looking for cost-effective flexible training to educate their workforce quickly and efficiently. Parallel to this is the accelerated demand for continuing professional development (CPD) brought about by the inception of the UKCC's Post-Registration Education and Practice Project (PREPP). Both registered and enrolled nurses are finding they need professional updating and skills and thus increased access to courses. The increased demand for education and training brought about by these changes cannot be met through traditional methods alone, requiring educational institutions to re-appraise their methods of delivery and introduce more flexible approaches to learning. There is every evidence that this is now the case with open learning, distance learning and flexible approaches to learning ever growing in popularity as providers of nurse education recognize the benefits such approaches offer. The emphasis is on meeting the diverse needs of the health care employers and individuals by providing education that is flexible, learner-centred and customer focused. This paper presents the findings of a national survey to ascertain how providers of flexible education plan educational programmes to meet the needs of their customers. Based on data collected from 120 educational institutions within the higher education, health and social care and private sectors, it highlights: the ways in which flexible learning programmes and courses are delivered; what aspects of flexibility are considered important when designing programmes to meet the needs of prospective customers; and what approaches are used to assess demand for flexible education. The study stresses the need for providers of flexible education to take into account the dual perspectives of those who have a stake in the flexibility of nurse education; NHS employers as funders of students and individual healthcare professionals themselves.
Previous studies have established that dopamine (DA) can stimulate phosphoinositide (PI) metabolism in the CNS and in the periphery. The present study summarizes our attempt to find a cell line that expresses this dopaminergic system. We describe that the stable clonal HN33.11 cell line, established by fusion of mouse hippocampal cells with neuroblastoma cells (N18TG2) that originate from A/J mouse, natively expresses the D1 DA receptor system that couples to PI hydrolysis. In this cell line, 500 microM DA or SKF38393 produced 43 and 75% increases in inositol phosphate (IP) accumulations, respectively. In contrast, noradrenaline or 5-hydroxytryptamine did not affect IP accumulations. The formation of IP that was stimulated by DA or SKF38393 was selectively blocked by the D1 DA receptor antagonist SCH23390 with IC50 values of 13 and 16 microM. This response was not mediated by the D1A DA receptor and was cyclic AMP-independent, as HN33.11 cells did not express this receptor, and DA or SKF38393 was unable to stimulate the formation of cyclic AMP. In Ca2+-free/100 microM EGTA medium, basal IP level was reduced by 31.5%, but SKF38393-stimulated PI hydrolysis was not affected. SKF38393-stimulated IP accumulation was also not affected by pertussis toxin (PTX) treatment (200 ng/ml), suggesting that this dopaminergic response is mediated by PTX-insensitive G proteins. Co-immunoprecipitation studies indicated that in membranes of HN33.11 cells, D1-like binding sites are coupled to G alpha(q) protein. Blockade of SKF38393-induced PI hydrolysis with antiserum against phospholipase C (PLC) isozymes, performed in permeabilized cells, as well as co-immunoprecipitation studies implicate PLCbeta3 and PLCbeta4 in this dopaminergically mediated PI hydrolysis cascade. The results indicate that HN33.11 cells express a D1-like DA receptor that couples to PLCbeta3/4 via G alpha(q) protein. These cells may therefore be a useful model system for investigating this receptor system.
Guidelines on the conduct of clinical trials of antibacterial agents produced by the US Food and Drug Administration, the British Society for Antimicrobial Chemotherapy, the Infectious Diseases Society of America and a European Working Party have been reviewed. Although very informative, these guidelines provide limited practical guidance on the design and statistical aspects of phase III studies of antimicrobial agents. This paper describes the differences between antibacterial trials and clinical studies in other therapeutic areas with regard to subjective endpoints, dual clinical and bacteriological endpoints, frequent protocol violations and difficulty of using placebo controls. The importance of a detailed protocol and planned analysis strategy is emphasized. The choice of comparator agents, practical issues with the blinding of trial materials and the documentation of patients excluded from study entry are discussed. The use of different patient groups and different endpoints in analyses are described. The principles of equivalence and their application to trials of antibacterial agents are discussed, together with an approach to calculating sample size. A variety of statistical analyses of results are compared for different situations indicating some of the problems that can arise. Different methods of presentation of study data are included with emphasis on regulatory submissions rather than scientific publications. Some graphical presentations are recommended and issues regarding data across different studies are discussed.
OBJECTIVE: To determine whether homeopathic Arnica 30X can reduce muscle soreness following long-distance running more than a placebo. DESIGN: Randomized, double-blind placebo-controlled trial. SETTING: Long-distance runs taking place in the community. SUBJECTS: A total of 519 runners anticipating delayed-onset muscles soreness after long-distance races. INTERVENTIONS: A homeopathic medicine (Arnica 30x) and an indistinguishable placebo. OUTCOME MEASURES: Subjects completed a visual analog scale and Likert scale of muscle soreness every morning and evening for the 5 days following their race. Race time was also recorded. The main outcome measure was mean 2-day visual analog scores. RESULTS: Results were obtained from 400 subjects. Groups were well matched at baseline. Mean 2-day visual analog soreness scores for Arnica and placebo were 45.2 mm and 41.0 mm, respectively. The 95% confidence interval was between 8.81 mm in favor of placebo and 0.51 mm in favor of Arnica. No differences were found for Likert scores or race time. CONCLUSION: Homeopathic Arnica 30x is ineffective for muscle soreness following long-distance running.
BACKGROUND: To review the outcome after restorative proctocolectomy among children and adolescents with ulcerative colitis at a pediatric inflammatory bowel disease center. METHODS: The records of all patients with ulcerative colitis undergoing colectomy and ileoanal anastomosis at The Hospital for Sick Children, Toronto, Canada, were reviewed. Questionnaires concerning functional results were sent to patients with restored transanal defecation. RESULTS: Seventy three patients (mean age, 13.2 years; range, 2.6-18.8 years) underwent ileoanal anastomosis (19 straight ileoanal anastomosis, 41 J pouch, 13 S pouch) between January 1980 and June 1995 and were observed 5.8+/-3.3 years. The ileoanal anastomosis is nonfunctional in 19 (26%) patients. Excision rates according to type of restorative procedure were J pouch, 7% (3 of 41); S pouch, 32% (4 of 13); and straight ileoanal anastomosis, 32% (6 of 19). Failure was usually attributable to intractable diarrhea among patients with straight ileoanal anastomosis but was caused by anastomotic leak or pelvic-perianal sepsis among patients with pouch procedures. Failure rates did not vary with age at ileoanal anastomosis. Among patients retaining ileoanal continuity, continence problems reported in the questionnaire were frequent and tended to be more extreme among younger patients. Overall, 90% of respondents reported satisfaction with the functional outcome of the restorative operation. CONCLUSIONS: The success rate of the ileoanal anastomosis/J-pouch procedure is comparable to that in adult series. The ileoanal anastomosis/J-pouch procedure is the operation of choice for children and adolescents who want ileoanal continuity restored after colectomy for ulcerative colitis.
It has been recognized for some time that bacterial species exist in complexes in subgingival plaque. The purpose of the present investigation was to attempt to define such communities using data from large numbers of plaque samples and different clustering and ordination techniques. Subgingival plaque samples were taken from the mesial aspect of each tooth in 185 subjects (mean age 51 +/- 16 years) with (n = 160) or without (n = 25) periodontitis. The presence and levels of 40 subgingival taxa were determined in 13,261 plaque samples using whole genomic DNA probes and checkerboard DNA-DNA hybridization. Clinical assessments were made at 6 sites per tooth at each visit. Similarities between pairs of species were computed using phi coefficients and species clustered using an averaged unweighted linkage sort. Community ordination was performed using principal components analysis and correspondence analysis. 5 major complexes were consistently observed using any of the analytical methods. One complex consisted of the tightly related group: Bacteroides forsythus, Porphyromonas gingivalis and Treponema denticola. The 2nd complex consisted of a tightly related core group including members of the Fusobacterium nucleatum/periodonticum subspecies, Prevotella intermedia, Prevotella nigrescens and Peptostreptococcus micros. Species associated with this group included: Eubacterium nodatum, Campylobacter rectus, Campylobacter showae, Streptococcus constellatus and Campylobacter gracilis. The 3rd complex consisted of Streptococcus sanguis, S. oralis, S. mitis, S. gordonii and S. intermedius. The 4th complex was comprised of 3 Capnocytophaga species, Campylobacter concisus, Eikenella corrodens and Actinobacillus actinomycetemcomitans serotype a. The 5th complex consisted of Veillonella parvula and Actinomyces odontolyticus. A. actinomycetemcomitans serotype b, Selenomonas noxia and Actinomyces naeslundii genospecies 2 (A. viscosus) were outliers with little relation to each other and the 5 major complexes. The 1st complex related strikingly to clinical measures of periodontal disease particularly pocket depth and bleeding on probing.
This investigation compared the site prevalence of 40 subgingival species in 30 periodontally healthy (mean age 36+/-9 years), 35 elders with a well-maintained periodontium (mean age 77+/-5) and 138 adult periodontitis subjects (mean age 46+/-11). Subgingival plaque samples were taken from the mesial aspect of each tooth (up to 28 samples) in the 203 subjects at baseline. The presence and levels of 40 subgingival taxa were determined in 5003 plaque samples using whole genomic DNA probes and checkerboard DNA-DNA hybridization. Clinical assessments including dichotomous measures of gingival redness, bleeding on probing, plaque accumulation and suppuration, as well as duplicate measures of pocket depth and attachment level, were made at 6 sites per tooth. The % of sites colonized by each species (prevalence) was computed for each subject. Differences in prevalence and levels among groups were sought using the Kruskal-Wallis test. Commonly detected species, such as Actinomyces naeslundii genospecies 2, Streptococcus sanguis and Streptococcus oralis did not differ significantly among subject groups. After adjusting for multiple comparisons, 4 species were significantly elevated and at greater prevalence in the periodontitis group. Mean % of sites (+/-SEM) colonized by Bacteroides forsythus was 10+/-3, 12+/-2 and 40+/-2 (p<0.001) for healthy, elder and periodontitis groups respectively. The odds ratio was 14.4:1 that a subject had periodontitis when B. forsythus was detected at > or = 5% of sampled sites. Mean prevalence for Porphyromonas gingivalis in healthy, elder and periodontitis subjects was 4+/-2, 5+/-2 and 23+/-2 respectively (p<0.001); for Treponema denticola 12+/-4, 10+/-3 and 30+/-2 (p<0.001) and for Selenomonas noxia 6+/-2, 7+/-2 and 19+/-2 (p<0.01). Similar differences among subject groups were observed when only sites with PD 0-4 mm were analyzed. The data suggest an etiologic role for B. forsythus, P. gingivalis, T. denticola and S. noxia in adult periodontitis.
The evolution of abnormal albumin excretion and its association with suggested risk factors were studied in 233 children with insulin dependent diabetes mellitus (IDDM) attending a single paediatric diabetic clinic over an eight year period. Yearly albumin:creatinine ratios (ACR; measured in mg/mmol) in early morning urine samples, glycated haemoglobin (HbA1c), and blood pressure were recorded. Thirty four (14.5%) children had a persistently raised ACR (ACR > or = 2.5 mg/mmol on at least three consecutive occasions) and 21 (9%) had an intermittently raised ACR (ACR > or = 2.5 mg/mmol on at least two occasions). Factors associated with a persistently raised ACR compared with normal albuminuria in IDDM included longer duration of diabetes, raised median HbA1c during the first five years after diagnosis, and final age adjusted systolic and diastolic blood pressure represented as standard deviation scores. The onset of persistently raised ACR in 13 of 34 children was before puberty and in 23 of 34 children it was within the first four years of diagnosis. The cross sectional prevalence of raised ACR was 12.9% at one year, 18.3% at five years, and 33% at 10 years after diagnosis. Raised ACR occurs frequently before puberty and in the early stages of childhood diabetes.
Cryptogenic fibrosing alveolitis is an interstitial lung disease of unknown etiology. Since pulmonary fibrosis is a recognized, if rare, complication of certain drug exposures, including antidepressants, betablockers, antibiotics, anticonvulsants, and nonsteroidal antiinflammatory drugs (NSAIDs), we tested the hypothesis that exposure to these drugs might contribute to the etiology of cryptogenic fibrosing alveolitis. Lifetime drug exposure data were collected from general practitioner records for 141 cases of cryptogenic fibrosing alveolitis and 246 age-, sex-, and community-matched control subjects from the Trent region of England. Additional data on lifetime smoking habits were obtained by postal questionnaire. The odds of disease in relation to ever exposure to antidepressants, betablockers, antibiotics, anticonvulsants, and NSAIDs were calculated by conditional logistic regression. For drug groups significantly associated with cryptogenic fibrosing alveolitis, subset analyses were performed to investigate the effects of individual drugs. Cryptogenic fibrosing alveolitis was associated with exposure to antidepressants (odds ratio [OR] 1.79 [95% CI 1.09-2.95], p = 0.022) and specifically to imipramine (OR 4.79 [1.50-15.3], p = 0.01), dothiepin (OR 2.37 [0.99-5.69], p = 0.05), and mianserin (OR 3.27 [1.11-9.61], p = 0.03). The magnitude of the overall effect of antidepressants was not changed by excluding all drug exposures within the 5 yr preceding the diagnosis of cryptogenic fibrosing alveolitis (OR 1.62 [0.94-2.77], p = 0.081), nor were the strong individual effects of imipramine (OR 5.72 [1.54-21.2], p = 0.009) and dothiepin (OR 5.58 [1.12-27.8], p = 0.036). These estimates were not appreciably affected by controlling for smoking history. The attributable risk for antidepressant exposure was in the region of 9-14%. No significant association was noted between cryptogenic fibrosing alveolitis and the four other drug groups in the primary hypothesis. The results of this study suggest that some antidepressant drugs can cause cryptogenic fibrosing alveolitis.
Hypophosphatemic rickets is commonly an X-linked dominant disorder (XLH or HYP) associated with a renal tubular defect in phosphate transport and bone deformities. The XLH gene, referred to as PHEX, or formerly as PEX (phosphate regulating gene with homologies to endopeptidases on the X-chromosome), encodes a 749-amino acid protein that putatively consists of an intracellular, transmembrane, and extracellular domain. PHEX mutations have been observed in XLH patients, and we have undertaken studies to characterize such mutations in 46 unrelated XLH kindreds and 22 unrelated patients with nonfamilial XLH by single stranded conformational polymorphism and DNA sequence analysis. We identified 31 mutations (7 nonsense, 6 deletions, 2 deletional insertions, 1 duplication, 2 insertions, 4 splice site, 8 missense, and 1 within the 5' untranslated region), of which 30 were scattered throughout the putative extracellular domain, together with 6 polymorphisms that had heterozygosity frequencies ranging from less than 1% to 43%. Single stranded conformational polymorphism was found to detect more than 60% of these mutations. Over 20% of the mutations were observed in nonfamilial XLH patients, who represented de novo occurrences of PHEX mutations. The unique point mutation (a-->g) of the 5'untranslated region together with the other mutations indicates that the dominant XLH phenotype is unlikely to be explained by haplo-insufficiency or a dominant negative effect.
Much has been written about the evaluation and management of mild brain trauma in sports. No less than 10 different 'guidelines' have been proposed and published to aid the clinician in the diagnosis of the condition. Too often, these guidelines have creating confusion instead of promoting an understanding of the spectrum of brain injury. As the understanding of the basic science of mild brain injury evolves, so must the approach to the concussed athlete. This article presents an up-to-date and clinically useful approach to the management of the athlete with a mild brain injury. The definition of 'concussion' is discussed and clarified and pertinent epidemiological data which highlight the importance of management skills as applied to athletes in a wide variety of sports are also reviewed. There is really no such thing as a 'mild concussion' if one considers the rare but catastrophic outcome of the second impact syndrome. For this reason, we review and expand upon the mechanisms of injury and pathophysiology. The accurate diagnosis of mild brain injury requires considerable experience, a high index of suspicion, a careful history and a series of examinations of the athlete, and a working knowledge of the athlete's personality and the likelihood of minimising their symptoms. The value of orientation questions pertinent to the athlete is now well established. Any focal neurological deficit or the deterioration of an athlete's condition warrants immediate hospitalisation, brain imaging and neurosurgical consultation. More commonly, athletes present with a brief alteration of consciousness, headache and amnesia and require careful examination and observation before returning to competition. The astute clinician will always err on the side of conservative management. The complete resolution of all symptoms before a return to play is imperative. Computerised tomography is very sensitive in the imaging of mild brain injuries. Neuropsychological testing is also very sensitive in the evaluation of brain injuries in athletes, and may become more clinically useful in the future.
In the US over one million persons are currently infected with the HIV, over half a million have had AIDS, and over 300,000 have died from AIDS. Worldwide, it is estimated that more than 17 million people are currently infected with HIV, and over 1,200,000 cases of AIDS have been reported to the World Health Organization. By some estimates, up to 40% of patients with AIDS will ultimately develop some form of cancer. Non-Hodgkin's lymphoma, Kaposi's sarcoma and invasive cervical cancer have a higher incidence in persons with HIV infection and all three are AIDS-defining illnesses. In addition, several reports suggest that a number of other malignancies may occur at an increased incidence in persons with HIV infection, including squamous-cell carcinoma of the head, neck and anus, plasmacytoma, melanoma, small-cell lung cancer, basal-cell cancer, and germ-cell tumours. Clinicians should become familiar with HIV-related malignancies as their incidence is expected to further increase as more effective therapies for HIV and associated opportunistic infections allow patients to live longer in an advanced state of immunodeficiency. In the current article, we will review the clinical and therapeutic aspects of the most common AIDS-related malignancies including non-Hodgkin's and Hodgkin's lymphomas, Kaposi's sarcoma and anogenital epithelial neoplasias.
The role of the transplant coordinator is multifaceted and demanding, requiring advanced clinical skills in addition to patient management responsibilities. Although much is known about the clinical skills of these coordinators, there is virtually no information available about their management abilities. A comparison of the beliefs of transplant coordinators and transplant staff nurses confirms that the coordinators have the role expectations and communication styles to allow them to function effectively in managing patient care as well as in working with physicians and other health professionals.
Although the early onset of Oppositional Defiant Disorder (ODD) is associated with an elevated risk of later psychopathology (including but not limited to conduct disorder and antisocial personality disorder), little is known about the factors influencing the course of this disorder in early life. In this article we first review data and theory from four conceptually-distinct domains of risk factors for disruptive disorders (child characteristics reflecting biologic vulnerabilities, parent-child attachment, parenting practices, and family adversity). Then we describe an empirical study that examined the power of these four domains (representing 10 specific risk factors) to predict the prognosis of clinic-referred, preschool boys with ODD; risk factors were assessed when these youngsters were first evaluated in the clinic and outcomes were measured 2 years later. The primary goal was to determine the unique importance of risk factors in the context of others examined simultaneously, a strategy that few previous studies have used. We found that the four-factor risk model predicted significant variance in mother's reports of externalizing (disruptive) behavior problems at the 2-year follow-up; however, the model did not predict teacher externalizing scores or clinicians' assessments of Diagnostic and Statistical Manual (DSM) disorders, as hypothesized. Analyses of specific factors within domains suggested that three were most consistently related to the negative outcomes of ODD boys: greater use of physical discipline by parents, greater life stress for families, and a greater number of pre- and perinatal complications. Nearly a third of the variance in mothers' reports of internalizing (inhibited) problems was attributable to two of these risk factors (life events stress and birth history) and to a third factor, delayed child development.