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Biomedical subjects

D Feinstein

Publications and source records attributed to D Feinstein.

At least 19 recordsLinked to original sources
PubMed2001

Diversity arrays: a solid state technology for sequence information independent genotyping.

Here we present the successful application of the microarray technology platform to the analysis of DNA polymorphisms. Using the rice genome as a model, we demonstrate the potential of a high-throughput genome analysis method called Diversity Array Technology, DArT'. In the format presented here the technology is assaying for the presence (or amount) of a specific DNA fragment in a representation derived from the total genomic DNA of an organism or a population of organisms. Two different approaches are presented: the first involves contrasting two representations on a single array while the second involves contrasting a representation with a reference DNA fragment common to all elements of the array. The Diversity Panels created using this method allow genetic fingerprinting of any organism or group of organisms belonging to the gene pool from which the panel was developed. Diversity Arrays enable rapid and economical application of a highly parallel, solid-state genotyping technology to any genome or complex genomic mixtures.

Blotting, Southern↗
PubMed2000

Video teleconferencing with realistic simulation for medical education.

This report describes how realistic patient simulation can be used with video teleconferencing to conduct long-distance clinical case discussions with realistic re-enactments of critical events. By observing what appears to be a real procedure unfolding in real time, it is intended that audience members will better learn and appreciate the lessons from conferences. A commercially available mannequin simulator and video teleconferencing technology were used in nine sessions between a free-standing simulation center and different conference sites throughout the U.S. Transmission was via high-speed telephone lines. In each conference, a clinical scenario was simulated on a screen. Audience members asked questions of a live simulated "patient" and family and later advised the care team on routine treatments and management of urgent clinical problems that arose during management of the mannequin simulator in a highly realistic clinical setting. Ninety-eight percent of respondents from one audience of 150 (response rate 60%) judged the quality of the presentation as "very good or excellent." In response to the statement that "the educational value of the presentation was much greater than that of a standard case conference," 95% scored 4 or 5 on a five-point Likert scale (where 5 is highest agreement). While all conferences were conducted successfully, there were instances of technical challenge in using teleconferencing technology. Technical information about the teleconferencing system and scenario preparation, contingency planning for failures, and other details of using this new teaching modality are described. Although audiences were enthusiastic in their response to this approach to clinical case conferences, further study is needed to assess the added value of interactive simulation for education compared to standard conference formats.

Education, Medical↗
PubMed1998

Metabolism of agmatine in macrophages: modulation by lipopolysaccharide and inhibitory cytokines.

Agmatine is an amine derived from the decarboxylation of arginine by arginine decarboxylase (ADC) and metabolized to putrescine by agmatinase. While prevalent in bacteria and plants, agmatine and its metabolic enzymes have been recently identified in mammalian tissues. In the present study we sought to determine: (a) whether macrophages (cell line RAW 264.7) express ADC and agmatinase, and (b) if the enzymes are regulated by lipopolysaccharide (LPS), and/or by the inhibitory cytokines transforming growth factor-beta (TGF-beta), interleukin-10 (IL-10) and interleukin-4 (IL-4). LPS induced a dose-dependent stimulation of agmatinase, while it decreased ADC, the effect in both cases being maximum at 20 h. As expected, LPS dose-dependently stimulated the inducible nitric oxide synthase activity (iNOS). A strong correlation was observed between the effects of LPS on the agmatine-related enzymes and iNOS. By contrast, exposure to IL-10 and TGF-beta caused a reduction in ADC and agmatinase, whereas IL-4 was ineffective on ADC, but reverted the LPS-induced increase of agmatinase. We conclude that the agmatine pathway may be an alternative metabolic route for arginine in macrophages, suggesting a regulatory role of agmatine during inflammation.

Agmatine↗
PubMed1998

The bacterial endotoxin lipopolysaccharide has the ability to target the brain in upregulating its membrane CD14 receptor within specific cellular populations.

Systemic injection of the bacterial endotoxin lipopolysaccharide (LPS) provides a very good mean for increasing the release of proinflammatory cytokines by circulating monocytes and tissue macrophages. There is now considerable evidence that LPS exerts its action on mononuclear phagocytes via the cell surface receptor CD14. The aim of the present study was to verify the hypothesis that the brain has also the ability to express the gene encoding the LPS receptor, which may allow a direct action of the endotoxin onto specific cellular populations during blood sepsis. Adult male Sprague-Dawley rats were sacrificed 1, 3, 6 and 24 h after systemic (i.v. or i.p.) injection of LPS or the vehicle solution. Brains were cut from the olfactory bulb to the medulla in 30-microm coronal sections and mRNA encoding rat CD14 was assayed by in situ hybridization histochemistry using a specific 35S-labeled riboprobe. The results show low levels of CD14 mRNA in the leptomeninges, choroid plexus and along blood vessels of the brain microvasculature under basal conditions. Systemic injection of the bacterial endotoxin caused a profound increase in the expression of the gene encoding CD14 within these same structures as well as in the circumventricular organs (CVOs) the organum vasculosum of the lamina terminalis, subfornical organ, median eminence and area postrema. In most of these structures, the signal for CD14 mRNA was first detected at 1 h, reached a peak at 3 h post-injection, declined at 6 h, and return to basal levels 24 h after LPS treatment. Quite interestingly, a migratory-like pattern of CD14 positive cells was observed from all sensorial CVOs to deeper parenchymal brain 3 and 6 h after LPS injection. At 6 h post-challenge, small positive cells were found throughout the entire parenchymal brain and dual-labeling procedure indicated that different cells of myeloid origin have the ability to express CD14 in response to systemic LPS. These included CVO microglia, choroid plexus and leptomeninge macrophages, parenchymal and perivascular-associated microglial cells, although specific nonmyeloid cells were also positive for the LPS receptor. These results provide the very first evidence of a direct role of LPS on specific cell populations of the central nervous system, which is likely to be responsible for the transcription of proinflammatory cytokines; first within accessible structures from the blood and thereafter through scattered parenchymal cells during severe sepsis.

Animals↗
PubMed1998

Methodologic standards for diagnostic test research in pulmonary medicine.

STUDY OBJECTIVES: To determine conformance with methodologic standards in the evaluation of diagnostic tests. DATA SOURCES: MEDLINE database search (1992 to 1997) of nine prominent general medicine and six subspecialty journals for articles that report discriminative properties of diagnostic tests in pulmonary medicine. STUDY SELECTION: Articles were eligible if they reported discriminative properties of diagnostic tests in humans, diagnostic tests were intended for the detection of existing conditions, and the target disorder was relevant to pulmonary medicine. DATA EXTRACTION: Each study was critically reviewed independently by two observers. DATA SYNTHESIS: Of the 1,029 retrieved articles, 41 met study inclusion criteria. The median number of the 12 major standards for design fulfilled by study articles was 6 (range, 1 to 12, 25th to 75th percentile, 5.0 to 8.5) and only 2 articles fulfilled all 12 standards. Seven (17%) articles did not report any standard measures of diagnostic accuracy and 7 (17%) provided data only for sensitivity and specificity. Only 4 of 17 articles (24%) that compared different tests used standard statistical methods. CONCLUSION: These results indicate that greater methodologic rigor is needed for studies that evaluate diagnostic tests in pulmonary medicine. Existing deficiencies in methodology risk the introduction of invalid tests into clinical practice.

Area Under Curve↗
PubMed1997

Personal mythology and psychotherapy: myth-making in psychological and spiritual development.

The sweeping changes and crises in the guiding myths of contemporary cultures provide the context of the individual's psychological and spiritual development. A five-stage process for facilitating the evolution of an individual's personal mythology is illustrated in a detailed case study, and the psychosocial tasks that must be accomplished to successfully navigate each stage are discussed.

Depression↗
PubMed1996

Neuropeptide Y receptor gene regulation in mouse adrenocortical Y-1 cells.

The mouse adrenocortical Y-1 cell line expresses a high level of neuropeptide Y1 receptor (NPY-Y1). Moreover the receptor density can be up-regulated by dexamethasone or down-regulated by cAMP. To determine whether such regulation occurs at the level of gene expression, Y1 receptor mRNA was measured using a reverse transcriptase-competitive PCR method. Dexamethasone treatment increased Y1 mRNA in Y-1 cells, whereas the cAMP and ACTH decreased it. We also observed that the amount of Y1 receptor RNA was unaffected by phorbol 12-myristate 13-acetate, a protein kinase C stimulator, but was abolished in a cell line expressing apolipoprotein E (apoE). The results indicated that NPY-Y1 receptor mRNA in Y-1 cells is highly regulated by several intracellular messengers. The role of apoE in such regulation is of particular interest in view of evidence that the isoform of the molecule is highly correlated to the age of onset of Alzheimer's disease. The effect observed in the Y-1 cell line which expresses apoE may implicate a possible role of this protein in the process of neuronal death that occurred in the Alzheimer's disease.

Adrenal Cortex↗
PubMed1996

Unresolved issues in laparoscopic splenectomy.

BACKGROUND: Laparoscopy is now expanding to surgery of intra-abdominal solid organs such as splenectomy for hematologic diseases. The purpose of this study is to further demonstrate that laparoscopic splenectomy is feasible for the surgeon, teachable for the resident, and beneficial to the patient and to revise prior contraindications to this minimally invasive approach. METHODS: Thirty-three consecutive cases of laparoscopic splenectomy were performed between May 1992 and March 1996. The series included 21 females and 12 males with a median age of 42 years (range 19-79) and a median weight of 73 kg (range 36-115). Indications included: immune thrombocytopenic purpura (20), hemolytic anemia (5), hereditary spherocytosis (4), infarction with abscess (1), Hodgkin's lymphoma (1), Gaucher's disease (1), and AIDS-related thrombocytopenia (1). Dissection was predominately performed with a new surgical instrument, the harmonic shears, and main vessels were controlled with clips. RESULTS: Thirty-two (97%) of the cases were completed laparoscopically, with 1 (3%) conversion to control hilar bleeding. Four patients underwent simultaneous cholecystectomy. The median spleen size was 13 cm (range 8-28) and median weight was 256 g (range 40-2100). Median operating time was 242 minutes (range 85-515). Morbidity occurred in 2 (6%) patients: ileus and small bowel obstruction. Median hospital stay was 4 days (range 2-14). There was no mortality in our series. Median follow-up was 20 months (range 1-46) with no evidence of late surgical complication or recurrent disease. CONCLUSION: Laparoscopic splenectomy may be successful in cases previously considered contraindicated, particularly splenomegaly and splenic infarct with abscess. It is a procedure that can be learned under appropriate guidance in academic centers.

Adult↗
PubMed1995

Anesthesia crisis resource management: real-life simulation training in operating room crises.

Little formal training is provided in anesthesiology residency programs to help acquire, develop, and practice skills in resource management and decision making during crises in practice. Using anesthesia crisis resource management (ACRM) principles developed at another institution, 68 anesthesiologists and 4 nurse-anesthetists participated in an ACRM training course held over a 2 and a half-month period. The anesthesia environment was recreated in a real operating room, with standard equipment and simulations requiring actual performance of clinical interventions. Scenarios included overdose of inhalation anesthetic, oxygen source failure, cardiac arrest, malignant hyperthermia, tension pneumothorax, and complete power failure. A detailed questionnaire was administered following the debriefing and completed by all participants, documenting their immediate impressions. Participants rated themselves as having performed well in the simulator. Senior attendings and residents rated themselves more highly than did their junior counterparts. The potential benefit of this course for anesthesiologists to practice anesthesia more safely in a controlled exercise environment, was rated highly by both groups. Over one half of respondents in all categories felt that the course should be taken once every 12 months; another third of each group felt that the course should be taken once every 24 months. While no senior attendings believed that the course should be taken once every 6 months, approximately 10% of respondents in other categories that it should. Of respondents in the senior and junior attending category, 5% felt the course should never be taken. Although attendings were less favorable than residents in their rating of the value of the course, both groups were still enthusiastic.

Anesthesia↗
PubMed1995

Staff support.

Staff support is essential for the individuals who care for patients with severe injuries. The loss of a colleague led to the development of the coping strategies described in this article. It is hoped that the experiences shared in this article will aid others in creating their own specific strategies for coping within hospitals or in other situations.

Burnout, Professional↗
PubMed1989

Neuronal modulation of Schwann cell glial fibrillary acidic protein (GFAP).

Adult rat sciatic nerves contain cytoskeletal peptides that resemble CNS glial fibrillary acidic protein (GFAP) in immunoreactivity and molecular weight. Immunohistological examination of teased nerve fascicles indicated that these peptides are expressed selectively by Schwann cells related to small axons. Radiolabelled mouse and rat CNS GFAP cDNA probes hybridized with a single, 2.7 kb RNA band in Northern blots prepared from total RNA from both rat sciatic nerve and rat brain. Sciatic nerve GFAP mRNA was detectable by this means in adult, 2 month, or 21 day postnatal rats, but not in 3,6, or 10 day postnatal rats. Sciatic nerve transection caused a marked reduction in the level of GFAP mRNA in the axotomized distal stump. We conclude that Schwann cell synthesis of GFAP is developmentally regulated and that Schwann cells, unlike astroglia, require continued trophic input from small axons in order to express GFAP.

Aging↗
PubMed1989

Onset of action between bupivacaine 0.5% and bupivacaine 0.5% plus fentanyl 75 mcg.

This study tested the hypothesis that the addition of fentanyl 75 mcg to bupivacaine 0.5% at the onset of epidural anesthesia for cesarean section reduces the onset time for T4 sensory blockade. The study was conducted in a randomized, double-blind fashion. The same observer performed sensory testing using pain to pinprick. Fourteen ASA I patients scheduled for elective cesarean section had epidural catheters placed. Group 1 (n = 7) received bupivacaine 0.5%, and group 2 (n = 7) received bupivacaine 0.5% plus fentanyl 75 mcg. Patients 5'0'' to 5'4'' in height received 15 ml, and patients 5'5'' to 5'9'' received 20 ml of bupivacaine. There were no adverse effects on the neonate or clinically important changes in maternal hemodynamics. The maternal age, height, weight, and bupivacaine dose did not differ between groups (p greater than 0.05). For group 1, the mean times for sensory loss at T7, T6, T5, and T4 were 13.1 +/- 3.8 minutes, 15.0 +/- 4.0 minutes, 16.9 +/- 4.3 minutes, and 19.3 +/- 4.9 minutes, respectively; for group 2, the mean times were 8.1 +/- 0.9 minutes, 9.9 +/- 1.1 minutes, 11.3 +/- 1.5 minutes, and 12.7 +/- 2.0 minutes, respectively. Two-factor analysis of variance between groups 1 and 2 showed a significant difference (p less than 0.0001), representing a 35% reduction of mean onset time. The coefficient of variation of the mean onset times for group 1 subjects was 26.6% +/- 1.7% and for group 2 subjects 12.7% +/- 2.2% (p less than 0.001), representing a 50% reduction in between-subject variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Acquired factor XI inhibitors in two patients with hereditary factor XI deficiency.

Two patients with hereditary factor XI deficiency developed inhibitors following plasma transfusions. Neither had severe spontaneous bleeding. The patients' plasmas neutralized both factor XI in plasma, purified factor XI, and purified factor XIa. The inhibitor in both patients' plasmas adsorbed to Protein A-Sepharose. The inhibitors eluted from Protein A-Sepharose were partially neutralized by kappa and lambda light chain antisera indicating that they were polyclonal IgG antibodies. Both inhibitors markedly decreased adsorption of factor XI to glass surfaces. The cleavage of factor XI by trypsin was unaffected by the inhibitors. The lack of severe spontaneous bleeding in both of these patients strongly suggests that an alternate coagulation mechanism bypassing factor XI must compensate for this severe defect.

Blood Coagulation Tests↗
PubMed1983

Increased fibrinolysis and amyloidosis.

We studied three patients with amyloidosis who had a significant hemorrhagic disorder secondary to increased fibrinolysis. In two of the three patients, bleeding was one of the major initial problems; in the other patient, bleeding occurred later in the course of the disease. All three patients were men with primary or myeloma-associated amyloidosis (ie, immunoglobulin-related or AL). None of the patients had significantly impaired liver function at the time of the diagnosis of increased fibrinolysis. At admission, fibrinogen levels were 60, 170, and 90 mg/dL in the three patients. All three patients had short euglobulin clot lysis times (less than 30 minutes) and evidence of in vitro clot lysis. One patient appeared to respond to aminocaproic acid (EACA). In patients with amyloidosis and bleeding, fibrinolytic tests should be done; in patients with increased fibrinolysis, a diagnosis of amyloidosis should be considered.

Adult↗
PubMed1981

Pseudo-factor-XI deficiency: effect of an inhibitor of factor XI adsorption to surface.

Recently we have described a normal plasma activity that modulates contact activation by inhibiting adsorption of factor XI to activating surfaces. Here we report the first identified case in which a patient has abnormal clotting tests due to an excess of a similar activity. The patient's plasma had a prolonged partial thromboplastin time and low apparent factor XI assay. His plasma prolonged the partial thromboplastin time of normal plasma and partially neutralized normal factor XI activity in vivo and in vitro. Analysis in dilute plasma revealed normal amounts of factor XI activity and antigen. Factor XI adsorption from plasma to activating surfaces was tested by adding a small amount of 125I-labeled purified factor XI to plasma, exposing the mixture to a glass tube or kaolin, and determining the amount of factor XI adsorbed to the surface. Whereas normal plasma and plasmas deficient in factor XII, factor XI, or Fletcher factor yielded about 4% adsorption to glass, factor XI adsorption from patient's plasma was less than 1%, indicating the presence of an adsorption inhibitor. This inhibitor did not affect factor XI activation or the activity of preformed factor XIa. It was not adsorbed by AI(OH)3 and was present in serum and the macroglobulin peak on gel filtration of the plasma through Sephadex G-200. The patient's history does not allow a definitive conclusion as to whether this inhibitor was associated with abnormal bleeding.

Adolescent↗