Biomedical subjects

C Nelson

Publications and source records attributed to C Nelson.

At least 37 records · Page 2Linked to original sources

PubMed1999

At-birth immunisation against hepatitis B using a novel pre-filled immunisation device stored outside the cold chain.

We evaluated the immunogenicity of hepatitis B (HB) vaccine in UniJect, a pre-filled, non-reusable injection device, stored at tropical temperatures for up to one month and used to give the first dose of HB vaccine to newborns. Infants in Tabanan district, Bali, Indonesia, were given their first dose of HB vaccine with UniJect stored out of the cold chain, UniJect stored in the cold chain; or standard syringe, needle and multidose vial stored in the cold chain. Subsequent doses were given by usual means and blood samples drawn 4-6 weeks after the third dose. No significant differences were found in seroconversion rates or geometric mean titres of HB surface antibody between the three groups.

Cold Temperature↗

PubMed1999

Race, gender, and partnership in the patient-physician relationship.

CONTEXT: Many studies have documented race and gender differences in health care received by patients. However, few studies have related differences in the quality of interpersonal care to patient and physician race and gender. OBJECTIVE: To describe how the race/ethnicity and gender of patients and physicians are associated with physicians' participatory decision-making (PDM) styles. DESIGN, SETTING, AND PARTICIPANTS: Telephone survey conducted between November 1996 and June 1998 of 1816 adults aged 18 to 65 years (mean age, 41 years) who had recently attended 1 of 32 primary care practices associated with a large mixed-model managed care organization in an urban setting. Sixty-six percent of patients surveyed were female, 43% were white, and 45% were African American. The physician sample (n = 64) was 63% male, with 56% white, and 25% African American. MAIN OUTCOME MEASURE: Patients' ratings of their physicians' PDM style on a 100-point scale. RESULTS: African American patients rated their visits as significantly less participatory than whites in models adjusting for patient age, gender, education, marital status, health status, and length of the patient-physician relationship (mean [SE] PDM score, 58.0 [1.2] vs 60.6 [3.3]; P = .03). Ratings of minority and white physicians did not differ with respect to PDM style (adjusted mean [SE] PDM score for African Americans, 59.2 [1.7] vs whites, 61.7 [3.1]; P = .13). Patients in race-concordant relationships with their physicians rated their visits as significantly more participatory than patients in race-discordant relationships (difference [SE], 2.6 [1.1]; P = .02). Patients of female physicians had more participatory visits (adjusted mean [SE] PDM score for female, 62.4 [1.3] vs male, 59.5 [3.1]; P = .03), but gender concordance between physicians and patients was not significantly related to PDM score (unadjusted mean [SE] PDM score, 76.0 [1.0] for concordant vs 74.5 [0.9] for discordant; P = .12). Patient satisfaction was highly associated with PDM score within all race/ethnicity groups. CONCLUSIONS: Our data suggest that African American patients rate their visits with physicians as less participatory than whites. However, patients seeing physicians of their own race rate their physicians' decision-making styles as more participatory. Improving cross-cultural communication between primary care physicians and patients and providing patients with access to a diverse group of physicians may lead to more patient involvement in care, higher levels of patient satisfaction, and better health outcomes.

Adult↗

PubMed1999

Stereoselective and substrate-dependent inhibition of hepatic mitochondria beta-oxidation and oxidative phosphorylation by the non-steroidal anti-inflammatory drugs ibuprofen, flurbiprofen, and ketorolac.

Non-steroidal anti-inflammatory drugs (NSAIDs) cause a range of adverse effects, some of which have been associated with perturbances of lipid metabolic pathways. Previous data demonstrating stereoselective formation of the CoA thioester of R-ibuprofen in particular were suggestive of possible stereoselective effects on lipid metabolism. Our aim was to characterise the relative stereoselectivity of the effects of ibuprofen, flurbiprofen, and ketorolac (0.01-1.0 mM) on both the beta-oxidation of palmitate and oxidative phosphorylation in rat hepatic mitochondria as a means of dissecting prostaglandin related from non-prostaglandin-related events. Beta-oxidation was inhibited stereoselectively by R-ibuprofen (P = 0.015), non-stereoselectively by R- and S-flurbiprofen (P = 0.002 and P = 0.004, respectively), and was essentially unaffected by either enantiomer of ketorolac. At 0.25 mM, inhibition by R-ibuprofen and both flurbiprofen enantiomers was partially reversed by increasing CoA concentrations (0-200 microM). Mitochondrial respiration was moderately inhibited by both enantiomers of ibuprofen and flurbiprofen (P < 0.01), but only by high concentrations (> or = 1 mM) of the enantiomers of ketorolac (P < 0.01). Uncoupling of oxidative phosphorylation measured as stimulation of State 4 respiration contributed to these effects. The data support interactions involving both stereoselective CoA-dependent and non-CoA-dependent mechanisms. The plasma drug concentrations required to achieve these effects are not likely to be attained in the majority of patients, although these concentrations are achievable in the gastrointestinal tract and may contribute to the well-known spectrum of adverse effects in this organ. Some patients do experience systemic adverse events which may be mediated by these mechanisms.

Animals↗

PubMed1999

Fibro-osseous lesions involving the brain: MRI.

We present the MRI findings in two patients with "fibro-osseous lesions" involving the central nervous system. A left temporal lobe mass was present in one patient and an extra-axial mass at the skull base in the other. In both cases, calcification was present, with low signal intensity on T1- and T2-weighted images.

Adult↗

PubMed1999

External cephalic version: predictors of success.

OBJECTIVE: To evaluate predictive variables for successful external cephalic version. METHODS: During 1987-1996, 128 women had external cephalic version attempts. Uterine tone, fetal spine position, breech location, breech type, gestational age, placental location, parity, maternal weight, amniotic fluid index, and estimated fetal weight were evaluated as predictors of success. RESULTS: Seventy-eight (64%) women were successfully converted from breech to vertex presentation. All subjects with low uterine tone had successful version. In women with high uterine tone, the combination of anterior or lateral fetal spine, noncornual placental location, and breech location out of the pelvis predicted success. Other independent variables associated with successful version included non-frank breech presentation, gestational age under 38 weeks, and parity of at least 1. CONCLUSION: Uterine tone may be the most important predictor of success when selecting candidates for external cephalic version.

Breech Presentation↗

PubMed1999

Targeting bcl-2 gene to delay androgen-independent progression and enhance chemosensitivity in prostate cancer using antisense bcl-2 oligodeoxynucleotides.

Bcl-2 expression is upregulated in prostate cancer cells after androgen withdrawal and is associated with the development of androgen independence and chemoresistance. Induction of apoptotic cell death after androgen ablation, or chemotherapy, may be enhanced through functional inhibition of bcl-2. In this report, we tested the effects of antisense bcl-2 oligodeoxynucleotides (ODN) with androgen ablation and taxane therapy on time to androgen-independent (Al) progression in the androgen-dependent Shionogi tumor model. Treatment of Shionogi tumor cells in vitro with 500 nmol/L antisense bcl-2 ODN decreased bcl-2 mRNA by 85%, compared with treatment with 500 nmol/L mismatch control ODN. Although bcl-2 expression levels in Shionogi cells were not changed by docetaxel treatment, docetaxel treatment induced bcl-2 phosphorylation. Consequently, the formation of bcl-2/Bax heterodimer formation was inhibited in a dose-dependent manner. Treatment of Shionogi tumors in vitro with either 500 nmol/L antisense bcl-2 ODN or 10 nmol/L docetaxel alone did not induce apoptosis or reduce growth rates. However, combined treatment reduced the concentration that reduces cell viability by 50% (IC50) of docetaxel from 100 nmol/L to 10 nmol/L and induced characteristic apoptotic DNA laddering and cleavage of the poly(ADP-ribose)polymerase (PARP) protein. Adjuvant in vivo administration of antisense bcl-2 ODN and polymeric micellar paclitaxel after castration resulted in a significant delay in time to Al recurrence when compared with administration of either agent alone. Furthermore, combined treatment of mice bearing Al recurrent Shionogi tumors with antisense bcl-2 ODN and micellar paclitaxel synergistically induced tumor regression and growth inhibition when compared with treatment with either agent alone. These findings suggest that down-regulation of bcl-2 by antisense ODN chemosensitizes Al Shionogi tumors to taxanes, over and above the effects of taxane-induced phosphorylation of bcl-2. Antisense bcl-2 ODN combined with taxanes may be a novel approach to the treatment of both established and emerging Al disease.

Androgens↗

PubMed1999

Startle potentiation by threat of aversive stimuli and darkness in adolescents: a multi-site study.

In recent years, the startle reflex has become an exciting new tool to investigate affective responses to aversive stimuli in humans. The popularity of this methodology is largely based on the substantial amount of animal research available on this topic. Several procedures have been developed to examine startle potentiation in humans, but most studies have been carried out in adults and may not be appropriate for children or adolescents. The present study is a multi-site project (Yale University, Harvard University, and the University of Minnesota) investigating two new procedures to examine the potentiation of startle in adolescents. The subjects were 50 male and female aged 13-17 years old. One procedure examined fear-potentiated startle to the threat of an unpleasant airblast directed to the larynx. The second examined the facilitation of startle in darkness. Potentiation was found using each procedure and the degree of potentiation was similar across laboratories. These results suggest that both the threat of an airblast and darkness can reliably be used to examine startle potentiation in young subjects.

Adolescent↗

PubMed1999

Maskless fabrication of light-directed oligonucleotide microarrays using a digital micromirror array.

Oligonucleotide microarrays, also called "DNA chips," are currently made by a light-directed chemistry that requires a large number of photolithographic masks for each chip. Here we describe a maskless array synthesizer (MAS) that replaces the chrome masks with virtual masks generated on a computer, which are relayed to a digital micromirror array. A 1:1 reflective imaging system forms an ultraviolet image of the virtual mask on the active surface of the glass substrate, which is mounted in a flow cell reaction chamber connected to a DNA synthesizer. Programmed chemical coupling cycles follow light exposure, and these steps are repeated with different virtual masks to grow desired oligonucleotides in a selected pattern. This instrument has been used to synthesize oligonucleotide microarrays containing more than 76,000 features measuring 16 microm 2. The oligonucleotides were synthesized at high repetitive yield and, after hybridization, could readily discriminate single-base pair mismatches. The MAS is adaptable to the fabrication of DNA chips containing probes for thousands of genes, as well as any other solid-phase combinatorial chemistry to be performed in high-density microarrays.

Base Sequence↗

PubMed1999

p53, mdm-2, and p21 waf-1 in the porokeratoses.

The etiology of the porokeratoses is unknown. Overexpression of the p53 tumor suppressor protein and disregulated cell cycle control have been pathogenically implicated. The p53 tumor suppressor gene product is regulated by mdm2 and both gene products influence cell cycle progression through the cyclin-dependent kinase inhibitor p21. Thirty-three cases of the various types of porokeratosis were immunohistochemically studied for p53, mdm2, and p21 proteins. Each of the cases showed increased p53 and decreased mdm2 and p21 expression within keratinocytes underlying cornoid lamella. This study confirms the previous findings of increased p53 staining and expands the potential roles of mdm2 and p21 in the pathogenesis of the porokeratoses.

Cyclin-Dependent Kinase Inhibitor p21↗

PubMed1999

Progression to androgen independence is delayed by adjuvant treatment with antisense Bcl-2 oligodeoxynucleotides after castration in the LNCaP prostate tumor model.

Bcl-2 has emerged as a critical regulator of apoptosis in a variety of cell systems and is up-regulated during progression to androgen independence in prostate cancer cells. The objectives of this study were to characterize changes in Bcl-2 after androgen withdrawal and during progression to androgen independence in the human prostate LNCaP tumor model and determine whether adjuvant use of antisense Bcl-2 oligodeoxynucleotides (ODNs) with androgen ablation delays progression to androgen independence. Bcl-2 expression in LNCaP cells is down-regulated to undetectable levels by androgen in vitro and up-regulated after castration in vivo. Antisense Bcl-2 ODN treatment reduced LNCaP cell Bcl-2 messenger RNA and protein levels by >90% in a sequence-specific and dose-dependent manner at concentrations >50 nM. Bcl-2 mRNA levels returned to pretreatment levels by 48 h after discontinuing treatment. Athymic male mice bearing SQ LNCaP tumors were castrated and injected i.p. with 12.5 mg/kg/day with two-base mismatch ODN control, reverse polarity ODN control, or antisense Bcl-2 ODN. Tumor volume in control mice gradually increased 5-fold (range, 3-6) by 12 weeks after castration compared to a 10-50% decrease in precastrate tumor volume in mice treated with antisense Bcl-2 ODN. Changes in serum PSA paralleled changes in tumor volume, increasing 4-fold faster above nadir in controls than in mice treated with antisense Bcl-2 ODN. After decreasing 70% by 1 week after castration, PSA increased 1.6-fold above precastrate levels by 11 weeks in controls while staying 30% below precastrate levels in antisense-treated mice. In a second group of experiments, LNCaP tumor growth and serum PSA levels were 90% lower (P<0.01) in mice treated with antisense Bcl-2 ODN compared with mismatch or reverse polarity ODN controls. These results support the hypothesis that Bcl-2 helps mediate progression to androgen independence and is an appropriate target for antisense therapy.

Androgens↗

PubMed1999

Sterilizable syringes: excessive risk or cost-effective option?

In recent years, many poorer countries have chosen to use disposable instead of sterilizable syringes. Unfortunately, the infrastructure and management systems that are vital if disposables are to be used safely do not exist. WHO estimates that up to 30% of injections administered are unsafe. The traditional sterilizable syringe had many disadvantages, some of which have been minimized through better design and the use of modern materials; others have been overcome because staff are able to demonstrate that they have performed safely. For example, the time-steam saturation-temperature (TST) indicator has enabled staff to demonstrate that a sterilizing cycle has been successfully completed. Health facility staff must be able to sterilize equipment, and the sterilizable syringe remains the least costly means of administering an injection. Data from countries that have acceptable systems for processing clinical waste indicate that safe and environmentally acceptable disposal, destruction and final containment cost nearly as much as the original cost of a disposable syringe. By careful supervision of staff behaviour and good management, some countries have demonstrated that they are able to administer safe injections with sterilizable syringes at a price they can afford.

Cost-Benefit Analysis↗

PubMed1999

National Ambulatory Medical Care Survey: 1995-96 summary.

OBJECTIVE: This report describes ambulatory medical care visits to nonfederally employed, office-based physicians in the United States during 1995 and 1996. Statistics are presented on selected physician, patient, and visit characteristics. METHODS: The data in this report were collected in the 1995 and 1996 National Ambulatory Medical Care Surveys (NAMCS). The NAMCS is part of the ambulatory care component of the National Health Care Survey (NHCS), which measures health care utilization across a variety of providers. The NAMCS is a national probability sample survey of visits to nonfederally employed, office-based physicians in the United States. Sample data were weighted to produce annual estimates. Estimates are presented in this report as annual averages unless otherwise noted. RESULTS: During 1995-96, an estimated 1.4 billion visits were made to physician offices in the United States, an annual average of 715.8 million visits. The visit rate was 2.7 visits per person per year. This rate did not differ significantly from visit rates observed in any previous survey year. Females made 59.4 percent of the visits, or 3.2 visits per person annually. This was higher than the visit rate for males. White persons had a higher visit rate than black persons. Six of every 10 visits were to primary care providers. Injury-related visits accounted for 11.8 percent of all office visits, or 84.6 million per year. The annual rate of injury-related office visits was 32.2 visits per 100 persons. The most frequent reason for visiting the physician was for a general medical examination (6.8 percent). Cough was the most frequent symptomatic reason. Acute respiratory infections and essential hypertension were the diagnoses reported most frequently.

Adolescent↗

PubMed1999

Strategies for safe injections.

In 1998, faced with growing international concern, WHO set out an approach for achieving injection safety that encompassed all elements from patients' expectations and doctors' prescribing habits to waste disposal. This article follows that lead and describes the implications of the approach for two injection technologies: sterilizable and disposable. It argues that focusing on any single technology diverts attention from the more fundamental need for health services to develop their own comprehensive strategies for safe injections. National health authorities will only be able to ensure that injections are administered safely if they take an approach that encompasses the whole system, and choose injection technologies that fit their circumstances.

Disposable Equipment↗

PubMed1998

Synaptic competition during the reformation of a neuromuscular map.

We have been studying the mechanisms whereby pools of motor neurons establish a rostrocaudal bias in the position of their synapses in some skeletal muscles. The serratus anterior (SA) muscle of the rat displays a rostrocaudal topographic map before birth, and the topography is re-established after denervation. In this report, we explore the potential role of synaptic competition between innervating axons as a means of generating topographic specificity. We followed the progress of the reformation of this map in neonatal animals under conditions that enhanced the likelihood of observing synaptic competition. This was accomplished by forcing caudal axons to regenerate ahead of rostral axons onto a surgically reduced SA muscle. In this way, caudal (C7) motor neurons had unopposed access to vacated synaptic sites on the remaining rostral half of the SA before the return of the rostral (C6) axons. Intracellular recording revealed that 2 d after the second denervation, most of the reinnervated end plates contained only axons from the C7 branch; the remaining reinnervated end plates received input from C6 only or were multiply innervated by C6 and C7 axons. After 6 d, the pattern was reversed, with most end plates innervated exclusively by C6. After 17 d, axons from C6 were the sole input to reinnervated end plates. During the transition from C7- to C6-dominated input, at end plates coinnervated by C6 and C7 axons, the average quantal content from C6 was the same as that from C7; after 7 d, the quantal content of C6 was greater than that of C7. We have thus developed an experimental situation in which the outcome of synaptic competition is predictable and can be influenced by the positional labels associated with axons from different levels in the spinal cord.

Animals↗

PubMed1998

Cytospin-enhanced direct immunofluorescence assay versus cell culture for detection of herpes simplex virus in clinical specimens.

The reliability of a cytospin-enhanced direct immunofluorescence assay (DFA), using Syva Micro Trak monoclonal antibodies, for detection of herpes simplex virus (HSV) was evaluated by comparing results with those of conventional cell culture. Of 250 clinical specimens, 64 were positive for HSV by cell culture, and 22 were positive by cytospin-enhanced DFA, two of which were negative by culture. The sensitivity, specificity, and positive and negative predictive values for cytospin-enhanced DFA were 31.25, 98.9, 90.9, and 80.7%, respectively. Cytospin-enhanced DFA is not an acceptable alternative to cell culture for detection of HSV.

Centrifugation↗

PubMed1998

Ropivacaine-induced seizure after extradural anaesthesia.

Ropivacaine is considered safer than bupivacaine, on the basis of experimental and human data that indicate a lower systemic toxicity. Here we report the occurrence of a single seizure after i.v. administration of ropivacaine 120 mg intended for extradural block in a patient having postpartum, tubal ligation. The only prodromal symptom was nervousness, and the only cardiovascular manifestation was sinus tachycardia. Systemic toxicity, although less than that expected with bupivacaine, can occur with ropivacaine.

Adult↗

PubMed1998

The value of orbital echography in orbital practice.

Twenty-three consecutive patients with orbital masses who were referred to a major medical center and later had biopsies underwent ophthalmic echographic evaluation. The efficacy of orbital echography was compared with both the clinical evaluation and other orbital imaging methods (computed tomography and magnetic resonance imaging). Echography was successful in all patients (100%) in detecting the orbital mass. The diagnosis was accurate in 18 of 22 patients (82%) echographically, 12 of 14 patients (86%) clinically, and 11 of 13 patients (85%) radiologically when a short differential was attempted. If all the patients examined were considered, echographic evaluation arrived at an accurate diagnosis in 18 of 23 patients (78%), clinical impression was accurate in 12 of 23 patients (52%), and radiologic evaluation was accurate in 11 of 20 patients (55%). In three patients, echography was the only imaging method used. The role of ophthalmic echography in the diagnosis of orbital masses is discussed.

Adult↗

PubMed1998

A population-based survey of Haemophilus influenzae type b nasopharyngeal carriage prevalence in Lombok Island, Indonesia.

BACKGROUND: The Haemophilus influenzae type b (Hib) nasopharyngeal carriage prevalence and invasive disease incidence rates are unknown in Indonesia; consequently Hib vaccine is not included in the routine vaccine schedule. METHODS: To determine carriage prevalence we conducted a population-based, island-wide prospective study of a systematic sample of 484 children 0 to 2 years of age in Lombok, Indonesia. We conducted a risk factor questionnaire and determined serotypes and antibiotic sensitivity patterns. RESULTS: We identified 155 H. influenzae isolates, of which 22 were type b and 12 were encapsulated but not type b. The age- and population-weighted Hib carriage prevalence, adjusted for the sampling design, was 4.6% (95% confidence interval, 3.7 to 5.5%). Children younger than 6 months of age had a carriage prevalence less than one-half that of older children, and carriage varied within the four administrative regions of the island; otherwise no risk factors for Hib carriage were identified. All Hib specimens were sensitive to ampicillin and 20 (91%) were sensitive to chloramphenicol. CONCLUSIONS: The Hib carriage prevalence in Lombok is similar to that found in developed countries before vaccine introduction. This suggests that further studies should proceed to determine whether Lombok has invasive disease rates as high as those that justified vaccine introduction in developed countries.

Carrier State↗