Search PubMed⌕ Search

Biomedical subjects

C Lancaster

Publications and source records attributed to C Lancaster.

At least 19 recordsLinked to original sources

Rare cancer cell analyzer for whole blood applications: automated nucleic acid purification in a microfluidic disposable card.

One current challenge facing point-of-care cancer detection is that existing methods make it difficult, time consuming and too costly to (1) collect relevant cell types directly from a patient sample, such as blood and (2) rapidly assay those cell types to determine the presence or absence of a particular type of cancer. We present a proof of principle method for an integrated, sample-to-result, point-of-care detection device that employs microfluidics technology, accepted assays, and a silica membrane for total RNA purification on a disposable, credit card sized laboratory-on-card ('lab card") device in which results are obtained in minutes. Both yield and quality of on-card purified total RNA, as determined by both LightCycler and standard reverse transcriptase amplification of G6PDH and BCR-ABL transcripts, were found to be better than or equal to accepted standard purification methods.

Fusion Proteins, bcr-abl↗

Rare cancer cell analyzer for whole blood applications: microcytometer cell counting and sorting subcircuits.

We demonstrate sorting of rare cancer cells from blood using a thin ribbon monolayer of cells within a credit-card sized, microfluidic laboratory-on-a-card ("lab card") structure. This enables higher cell throughput per minute thereby speeding up cell interrogation. In this approach, multiple cells are viewed and sorted, not individually, but as a whole cell row or section of the ribbon at a time. Gated selection of only the cell rows containing a tagged rare cell provides enrichment of the rare cell relative to background blood cells. We also designed the cell injector for laminar flow antibody labeling within 20s. The approach combines rapid laminar flow cell labeling with monolayer cell sorting thereby enabling rare cell target detection at sensitivity levels 1000 to 10,000 times that of existing flow cytometers. Using this method, total cell labeling and data acquisition time on card may be reduced to a few minutes compared to 30-60 min for standard flow methods.

Antigens, CD34↗

Interstitial microwave thermoablation for localized prostate cancer.

The conventional treatment for localized prostate cancer can be associated with significant morbidity and cost. Interstitial microwave thermoablation is a minimally invasive procedure used experimentally to treat selected patients with failed radiation therapy of prostate cancer at our institution. Preliminary results in these patients suggest that this treatment might be a useful alternative in selected patients with previously untreated localized prostate cancer. In this report we describe the first use of percutaneous transperineal interstitial microwave thermoablation to treat a case of primary prostate cancer. There were no treatment complications. At 18 months the patient's serum prostate-specific antigen remains undetectable, and his prostate biopsy shows no evidence of malignancy. These very preliminary but exciting results in this single patient suggest that this experimental technique should be explored further.

Aged↗

Differences in curriculum emphasis in US undergraduate and generalist residency education programmes.

OBJECTIVES: Little attention has been paid to the differential emphasis undergraduate and graduate medical education programmes place on the broad competencies that will be needed for practice in an increasingly managed health care environment. The purpose of this study was to determine differences in emphasis that undergraduate and primary care graduate medical education programmes are currently placing on 33 broad practice competencies, compared with the emphasis they ideally would like to give them, and the barriers they perceive to curriculum change. DESIGN: Subjects were surveyed by mailed questionnaire. A reminder postcard and follow-up mailing were sent to non-respondents. SETTING: US allopathic medical schools. SUBJECTS: Academic deans identified by the Association of American Medical Colleges (AAMC) and generalist (family medicine, internal medicine, paediatrics and obstetrics-gynaecology) residency programme directors identified by the American Council on Graduate Medical Education (ACGME). RESULTS: Findings revealed that residency programmes placed greater emphasis on the study's broad curriculum topics than did undergraduate medical education programmes. Statistically significant differences were found in current emphasis for 12 topics and ideal emphasis for six topics. Both groups identified an already crowded curriculum and inadequate funding as the top two barriers to curriculum change. CONCLUSIONS: The differences in curriculum emphases and perceived barriers to curriculum change most probably reflect the different realities of undergraduate and graduate medical education programmes, i.e. academics vs. a focus on immediate practice realities.

Curriculum↗

Microwave Thermoablation for Localized Prostate Cancer After Failed Radiation Therapy: Role of Neoadjuvant Hormonal Therapy.

The treatment of residual prostate cancer after irradiation is often associated with significant morbidity and a high failure rate. Percutaneous transperineal interstitial microwave thermoablation is a minimally invasive procedure used experimentally in our institution to treat selected patients with failures of external-beam radiation therapy for prostate cancer. The aim is to ablate all residual intraprostatic cancer thermally. Patients were treated under general or epidural anesthesia with transrectal ultrasound guidance of transperineal placement of the microwave antennas. The rectum, urethra, and a developed space between the prostate and surrounding tissues were actively cooled. The minimal target temperature of the prostate was 65 degrees C for 15 min. The temperature was measured in all cases with interstitial prostatic thermosensors and in selected cases with online magnetic resonance scanning. Thirty-seven patients with apparently localized prostate cancer after failure of treatment for cure with external-beam therapy were subjected to this treatment, and 20 of these patients have at least 12 months of follow-up. The initial prostate specific antigen (PSA) concentration ranged from 0.2 to 120 ng/mL. At 12 months, 12 of 20 patients had no biochemical or histologic evidence of disease, and 11 of 14 patients with initial PSA concentration <10 ng/mL had no evidence of disease. Five of the thirty-seven patients were treated with 3 months of neoadjuvant androgen ablation because the volume of their prostates precluded adequate heating. The average volume decline was 28%, which allowed all men to be treated. Two of these patients have been followed for at lease 1 year, and neither shows evidence of recurrence. Side effects of treatment in all patients were modest. Preliminary results suggest that this treatment might be useful in selected patients as a salvage therapy after failure of radiation therapy for localized prostate cancer.

Journal Article↗

The relationship of various measures of time urgency to indices of physical health.

The degree of association with two general health indices was assessed for three separate measures of time urgency. The Speed and Impatience subscale of the Jenkins Activity Survey was found to have no significant relationships with the health indices. The Time Urgency/Perpetual Activation (TUPA) scale, as well as the Irritability and Impatience scale, did correlate in comparable ways with a majority of the health indicators. A very brief, 2-item impatience subscale of the Irritability and Impatience Scale also correlated with health indices in essentially the same manner as the complete Irritability and Impatience Scale and the TUPA Scale. It was concluded that because of its convenience of administration, the very brief 2-item impatience subscale of the Irritability and Impatience Scale may constitute the instrument of choice for assessing time urgency as it relates to noncardiovascular health. A question is raised regarding whether anger and time urgency constitute separate factors or are aspects of a single behavioral trait.

Adolescent↗

Effective nonsteroidal anti-inflammatory drugs devoid of gastrointestinal side effects: do they really exist?

All nonsteroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal (GI) side effects. One focus of development was to design new drugs with reduced propensity for GI damage. With aspirin as the prototype, research efforts to develop NSAIDs with the efficacy but not the gastroduodenal damaging effects of aspirin have been partially successful. Techniques used to minimize gastric irritant potential include developing new drug classes, enteric coatings, nonacidic drugs, and prodrugs. Properties associated with the mucosal damaging effects of NSAIDs (potent inhibition of prostaglandin synthesis, solubility at low pH, and acid characteristic) are not found in the newer prodrugs such as droxicam and nabumetone. Droxicam was developed as a prodrug of piroxicam with equal efficacy, in addition to improved GI tolerance. Prodrugs may offer new molecules with pharmacological profiles and efficacy to toxicity ratios more acceptable to clinicians and patients alike.

Anti-Inflammatory Agents, Non-Steroidal↗

Implementation and evaluation of a computer-based preventive services system.

BACKGROUND AND OBJECTIVES: Insufficient attention has been paid to the role that modern information systems can play in improving the delivery of and education about preventive services in family medicine training and practice sites. From September 1990-September 1993, the Department of Family Medicine at the Medical University of South Carolina conducted a demonstration project designed to develop, implement, and evaluate a comprehensive, computer-based preventive services delivery and educational system, based on the recommendations in the US Preventive Services Task Force (USPSTF) Report. METHODS: A computer-based patient record (CPR) system was implemented. The system had sophisticated preventive services tracking and reminder, physician, and patient education features. Twenty-nine basic USPSTF recommendations were incorporated in the system. An extensive physician education series was also implemented. A multi-method evaluation system, including patient exit surveys, physician interviews, and practice audits was used to evaluate and design improvements to the CPR and education systems. RESULTS: Although the system initially had no effect on patient perceptions about the frequency of preventive services delivery, there was reasonable concordance between patient desires and physician behavior for the discussion of preventive services (Kappa = .5 to .6). Physician acceptance of the system was good--in 1992, 30% of physicians used the preventive services reminders in most of their patient visits, and in 1993, 88% of physicians reported more frequent use. Practice audits from February 1992-July 1993 showed increased adherence with all seven counseling services, 10 of 15 screening services, and one of five immunization services. CONCLUSIONS: A CPR-based preventive services system coupled with an adaptable physician education about and delivery of preventive services. an ideal solution to improving the education about and delivery of preventive services.

Adolescent↗

Gender-related subcomponent differences in high type A subjects.

Thirty Type A males and 30 Type A females were administered an expanded version of the Structured Interview designed to assess 11 Type A subcomponents. The purpose was to determine whether males and females follow different subcomponent routes in achieving their Type A status. As predicted, males scored higher than females on two of four anger-related variables. Contrary to prediction, males scored higher than females on the subcomponent of exaggerated social control. These findings were interpreted as providing some support for the notion of differing gender-related subcomponent routes for achieving Type A status. These findings also may have implications for the higher incidence of coronary heart disease in high TABP males vs. females.

Adolescent↗

Formulation and intestinal absorption enhancement evaluation of water-in-oil microemulsions incorporating medium-chain glycerides.

We developed self-emulsifying water-in-oil (w/o) microemulsions incorporating medium-chain glycerides and measured their conductance, viscosity, refractive index and particle size. Formulation of Calcein (a water-soluble marker molecule, MW = 623), or SK&F 106760 (a water-soluble RGD peptide, MW = 634) in a w/o microemulsion having a composition of Captex 355/Capmul MCM/Tween 80/Aqueous (65/22/10/3, % w/w), resulted in significant bioavailability enhancement in rats relative to their aqueous formulations. Upon intraduodenal administration the bioavailability was enhanced from 2% for Calcein in isotonic Tris, pH 7.4 to 45% in the microemulsion and from 0.5% for SK&F 106760 in physiological saline to 27% in the microemulsion formulation. The microemulsion did not induce gross changes in GI mucosa at a dosing volume of 3.3 ml/kg. These results suggest that water-in-oil microemulsion systems may be utilized for enhancement of intestinal drug absorption.

Absorptiometry, Photon↗

Introducing the Objective Structured Clinical Examination to a family practice residency program.

BACKGROUND: The Objective Structured Clinical Examination (OSCE) is a multiple station examination where examinees are expected to demonstrate mastery of a competency within a specified time at each station. It is commonly used to evaluate medical students and is less often used in residency programs. This paper describes the process of introducing a 12-station OSCE to a university-based family practice residency program. METHODS: The examination evaluated cognitive, psychomotor, and behavioral competencies in 31 residents. The 10-minute stations included: two simulated patients; two skills demonstrations; six modified essay questions, four in response to a written scenario and two in response to a video trigger; and two rest stations. Feedback was given in a large group at the conclusion of the examination. RESULTS: Construct validity was demonstrated by increasing scores with training year; concurrent validity was demonstrated by significant correlations of the OSCE scores with the American Board of Family Practice in-training examination scores and the residents' monthly rotation evaluation scores. Reliability was demonstrated by significant correlation between the scores of the OSCE and its subsets. CONCLUSIONS: As a method of formative evaluation, the OSCE had an overall positive response from residents and faculty.

Clinical Competence↗

Gastric cytoprotection by intracisternal interleukin-1 beta in the rat.

The effects of intracisternal (ic) injection of recombinant interleukin-1 beta (IL-1) on absolute ethanol-induced gastric necrotic lesions were studied in conscious rats. IL-1 given ic inhibited ethanol-induced gastric lesions. The cytoprotective effect was dose dependent (ED175 ng/rat), long lasting with a maximal action when given 1-3 h prior to ethanol, blocked by ic injection of a IL-1 receptor antagonist protein (IRAP), and by intraperitoneal injection of indomethacin. IL-1, injected ic, was detected in the peripheral blood. However, IL-1 serum levels were lower after IL-1 injection ic than after ip at a dose giving equal gastric protection. These data show that ic IL-1 induces long lasting gastric protection mediated by interaction with IL-1 receptors and prostaglandin pathways at central and/or peripheral sites that remain to be localized.

Animals↗

Interleukin-1 is cytoprotective, antisecretory, stimulates PGE2 synthesis by the stomach, and retards gastric emptying.

Human recombinant interleukin 1 beta (IL-1) administered intraperitoneally to rats produced the following gastric effects: 1. It was cytoprotective, preventing gastric mucosal necrosis produced by oral administration of one ml of absolute ethanol to fasted animals. The ED50 was 1200 units/kg (110 ng per animal). IL-1 was 125 times more potent than prostaglandin E2 (on a weight basis), and 6,000 times more potent (on a molar basis). 2. The cytoprotective effect of IL-1 was blocked by indomethacin (inhibitor of prostaglandin synthesis) and by IRAP (a specific interleukin-1 receptor antagonist protein). IRAP did not inhibit cytoprotection induced by PGE2. 3. IL-1 prevented the formation of gastric erosions induced by aspirin. 4. IL-1 inhibited gastric secretion (volume, acid concentration and output), in the pylorus-ligated rat, with an ED50 of 300 units/kg (3.2 ng per animal). 5. Indomethacin and IRAP blocked the antisecretory effect of IL-1. 6. IL-1 retarded gastric emptying, an effect blocked by IRAP, but not by indomethacin. 7. IL-1 increased synthesis of prostaglandin E2 by the gastric mucosa by 111%. IL-1 is the most potent of known agents that are gastric cytoprotective, antiulcer, antisecretory, and delay gastric emptying. It appears to act mostly by stimulating the synthesis of prostaglandins by the stomach. These studies suggest that the stomach possesses IL-1 receptors. These are probably located on parietal cells (that produce acid), on prostaglandin-producing cells, on smooth muscle cells (responsible for gastric emptying), and on as yet unidentified cells involved in gastric cytoprotection. Both IL-1 and IRAP, being natural substances, may play a physiological role in the maintenance of gastric mucosal integrity, and in the regulation of acid secretion and gastric motility.

Animals↗

Prevention by prostaglandins of caerulein-induced pancreatitis in rats.

Acute edematous pancreatitis was produced in rats by subcutaneous administration of caerulein. Pancreas weight, pancreas histology and plasma amylase were used as endpoints to quantitate the severity of the syndrome. A caerulein dose of 10 micrograms/kg.hour produced the most severe pancreatitis, whereas at 5 micrograms/kg.hour the values were half-maximal. The pancreatic lesions were characterized by edema, formation of cytoplasmic vacuoles, leukocytic infiltration, necrosis, and with time (12-hour caerulein infusion) dilated acini. Cholecystokinin octapeptide also produced pancreatitis when given at ten times the dose required for caerulein (50 micrograms/kg.hour instead of 5 micrograms/kg.hour). Carbachol did not induce pancreatitis. Two prostaglandins, 16,16-dimethyl prostaglandin E2 injected subcutaneously and prostaglandin E2 infused subcutaneously, dose dependently prevented caerulein-induced pancreatitis (pancreatic edema, leukocytic infiltration, and necrosis) and reduced the number and size of intracellular vacuoles. The ED50 were 15 to 25 micrograms/kg for 16,16-dimethyl prostaglandin E2 and 90 micrograms/kg.hour for prostaglandin E2. Neither prostaglandin, given at doses inhibiting the development of pancreatitis, prevented the retardation of gastric emptying caused by caerulein, a finding suggesting that the prostaglandins may act specifically on the effect of caerulein on the pancreas but not on caerulein receptors in gastric smooth muscle. Indomethacin, an inhibitor of prostaglandin synthesis, and methscopolamine bromide, an anticholinergic agent, had no effect on caerulein-induced pancreatitis. We concluded that prostaglandins of the E type prevent the development of caerulein-induced pancreatitis. The mechanism by which prostaglandins protect the pancreas may involve stabilization of lysosomes within the acinar cells and inhibition of intracellular activation of pancreatic digestive enzymes.

16,16-Dimethylprostaglandin E2↗

Indomethacin-induced gastric antral ulcers in hamsters.

Antral ulcers account for about half of gastric ulcers in humans. An animal model was developed to produce such ulcers. Indomethacin given subcutaneously to normally fed hamsters produced antral ulcers within 1-5 h, dose dependently. These ulcers penetrated the muscularis mucosae. With repeated administration of indomethacin and longer duration of treatment, the lesions became more severe and most animals died with perforated antral ulcers after 2-5 days. Like indomethacin, aspirin given orally also produced antral ulcers in hamsters. Indomethacin reduced the formation of prostaglandin E2, prostaglandin F2 alpha, and 6-keto prostaglandin F1 alpha by the antral mucosa, and increased gastric acid output more than twofold. The ulcers were prevented by various antisecretory agents (cimetidine, methscopolamine bromide, and omeprazole), and the antiulcer dose of each of these agents corresponded to the antisecretory dose. By contrast, several prostaglandins prevented the ulcers at very low, nonantisecretory doses. 16,16-Dimethyl prostaglandin E2 prevented the ulcers at a dose nearly 3000 times lower than the gastric antisecretory ED50. The mechanism by which prostaglandins prevent formation of these ulcers is unknown, but the effect is consistent with cytoprotection, i.e., protection of the gastric mucosa by nonantisecretory doses. Indomethacin-induced antral ulcers appear to depend on two factors: a depletion of prostaglandin content of the antrum and gastric hyperacidity.

Administration, Oral↗

The current status of undergraduate urological teaching.

At the request of the Society of University Urologists a survey of urological teaching at 113 United States medical schools was done. The most distressing finding was that more than two-thirds (68 per cent) of the schools do not require any clinical exposure to urology before graduation. In view of the fact that urology is rarely, if ever, taught in any of the primary care disciplines after graduation, it is suggested that patient care may well suffer for this shortcoming in our medical education curriculum.

Curriculum↗

Effect of 16,16-dimethyl PGE2 on renal papillary necrosis and gastrointestinal ulcerations (gastric, duodenal, intestinal) produced in rats by mefenamic acid.

Mefenamic acid, given orally to rats at a single dose of 1200 mg/kg, produced renal papillary necrosis (RPN) in 63% of animals. The incidence was reduced to 27% by 16,16-dimethyl PGE2 (dmPGE2), given at an oral dose of 0.75 mg/kg t.i.d. RPN is likely to be caused by the renal prostaglandin depletion elicited by mefenamic acid, an inhibitor of prostaglandin cyclooxygenase. Substitution with dmPGE2 reduces RPN presumably by preventing the prostaglandin depletion. We conclude that the prostaglandin used is cytoprotective for the kidney. Mefenamic acid, like most nonsteroidal anti-inflammatory compounds (NOSAC), produced ulcerations of the small intestine (jejunum and ileum). These were prevented by dmPGE2 (intestinal cytoprotection). Unlike most other NOSAC, however, mefenamic acid produced duodenal ulcers in nearly all animals (80%). Of these ulcers, 88% were perforated. Twenty-five of the twenty-six animals that died had a perforated ulcer. These duodenal ulcers were also prevented by dmPGE2. Mefenamic acid-induced ulcers could be used as an experimental model for testing agents with a potential for preventing or healing duodenal ulcers.

16,16-Dimethylprostaglandin E2↗