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PubMed1991

The involvement of excitatory amino acids in neocortical epileptogenesis: NMDA and non-NMDA receptors.

Conventional intracellular recording techniques were used to investigate the N-methyl-D-aspartate (NMDA) and non-NMDA mediated synaptic mechanisms underlying the stimulus-induced paroxysmal depolarization shift (PDS) generated by cells in rat neocortical slices treated with bicuculline methiodide (BMI). The NMDA receptor antagonists CPP or MK-801 were ineffective in abolishing the PDS. However, both drugs were able to attenuate the late phase of the PDS and delay its time of onset. In contrast, the non-NMDA receptor blocker CNQX demonstrated potent anticonvulsant property by reducing the PDS into a depolarizing potential that was graded in nature. This CNQX-resistant depolarizing potential was readily blocked by CPP. Voltage-response analysis of the PDS indicated that the entire response (including its NMDA-mediated phase) displayed conventional voltage characteristics reminiscent of an excitatory postsynaptic potential that is mediated by non-NMDA receptors. We conclude that the activation of non-NMDA receptors is necessary and sufficient to induce epileptiform activity in the neocortex when the GABAergic inhibitory mechanism is compromised. The NMDA receptors contribute to the process of PDS amplification by prolonging the duration and reducing the latency of each epileptiform discharge. However, the participation of NMDA receptors is not essential for BMI-induced epileptogenesis, and their partial involvement in the PDS is dependent upon the integrity of the non-NMDA mediated input. The lack of NMDA-like voltage dependency observed in the PDS's late phase might reflect an uneven distribution of NMDA receptors along the cell and/or an association of this excitatory amino acid receptor subtype in the polysynaptic pathways within the neocortex.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1991

Afterpotentials following penicillin-induced paroxysmal depolarizations in rat hippocampal CA1 pyramidal cells in vitro.

Epileptic discharges were induced by superfusion of rat hippocampal slices with penicillin. Under these conditions the neurons generated paroxysmal depolarization shifts (PDS) after electrical stimulation of Schaffer collaterals. The PDS were followed by large afterhyperpolarizations lasting about 2 s. The mechanisms causing these afterhyperpolarizations were studied in CA1 pyramidal cells. A late component of the afterhyperpolarizations, which determined their overall duration, was blocked by intracellular application of EGTA and reduced by superfusion with 8-Br-cAMP. In the same neurons these drugs had a comparable effect on afterhyperpolarizations following depolarizing current injections; it was therefore concluded that the late component of the PDS afterhyperpolarizations was caused by a slow Ca2(+)-activated K+ current. An initial fast component of PDS afterhyperpolarizations, which peaked about 60 ms after PDS onset, was reduced by EGTA but not affected by 8-Br-cAMP suggesting that the fast Ca2(+)-activated K+ current also contributed to the PDS afterhyperpolarizations. Superfusion of the slice with the gamma-aminobutyric acid B receptor (GABAB) antagonists phaclofen or 5-aminovalerate reduced the amplitude of the afterhyperpolarizations during the first 1000 ms but did not affect the late Ca2(+)-dependent component, indicating that a GABAB-mediated K+ inhibitory postsynaptic potential (IPSP) contributed to the PDS afterhyperpolarization. Intracellular injection of Cl- revealed that an early part of the afterhyperpolarizations lasting about 500 ms was Cl(-)-dependent. This component was blocked by superfusion of the slices with bicuculline, suggesting that a GABAA-mediated Cl- IPSP contributed to the PDS afterhyperpolarization.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

Further indications for genetic heterogeneity of euthyroid familial goiter.

Iodine deficiency is the most important etiological factor for euthyroid endemic goiter. However, family and twin pair studies also strongly indicate a genetic prediposition. In euthyroid goiters molecular defects in the thyroglobulin (TG), and Na+/I- symporter (NIS) gene have been identified. Numerous mutations in the Pendrin (PDS) gene have been found in families with PDS characterized by deafness and euthyroid goiter. Moreover, family studies indicated two major candidate loci MNG-1 on chromosome 14q31 and Xp22. However, all previous linkage studies investigated only one family. To clarify the general relevance of these previously identified two major candidate loci for the etiology of euthyroid goiter we investigated four families with a total number of 74 family members by linkage analysis with microsatellite markers. Moreover, we analyzed the thyroid candidate genes TG, thyroperoxidase (TPO), NIS, TSH receptor, and PDS. In a further family with 12 members in whom we have previously demonstrated linkage to the MNG-1 locus we investigated the Xp22 locus and the PDS gene in addition to our initial study. Linkage analysis results of our study are not significant enough to definitely exclude or confirm linkage to the investigated candidate genes and loci. Nevertheless, we obtained very weak indications for possible linkage to Xp22 in one family by a maximal multipoint LOD score of 1.15, and cosegregation of haplotypes among affected family members. Moreover, in another family linkage to PDS was indicated by a maximal multipoint LOD score of 1.87 as well as cosegregation of haplotypes. However, sequencing of the PDS gene did not reveal germline mutations. A significant total NPL score of 6.5 for PDS over all families most likely indicated linkage to a genomic region close to PDS. Furthermore, the likelihood of linkage to MNG-1 and Xp22 is reduced, because multipoint LOD scores were below 1 or negative. In all families there was no significant evidence for linkage for the thyroid candidate genes TG, TPO, NIS, or the TSH receptor. In conclusion, a general role of MNG-1 and Xp22 for the etiology of euthyroid goiter is unlikely but cannot clearly excluded. The multipoint parametric and nonparametric LOD scores further suggest genetic heterogeneity in the etiology of familial euthyroid goiter. To identify other susceptibility loci it is necessary to perform genome-wide linkage analysis studies with more families.

Adolescent↗
PubMed2005

Genetic heterogeneity for autosomal recessive pyridoxine-dependent seizures.

Pyridoxine-dependent seizure (PDS) is a rare autosomal recessive intractable seizure disorder only controlled by a daily supplementation of pharmacological doses of pyridoxine (Vitamin B6). Although glutamate decarboxylase utilizes pyridoxal phosphate as a cofactor during conversion of the excitatory amino acid, glutamate, to the inhibitory neurotransmitter, gamma-amino butyric acid (GABA), several studies have failed to demonstrate a linkage to either of the glutamate-decarboxylase-encoding genes (GAD1 and GAD2) and PDS excluding involvement of this functional candidate. However, in 2000, a locus for PDS was mapped to a 5 cM interval at chromosome 5q31 in four consanguineous and one multisib pedigree (Z(max)=8.43 at theta=0 for marker D5S2017) [Cormier-Daire et al. in Am J Hum Genet 67(4):991-993 2000]. We undertook molecular genetic studies of six nonconsanguineous North American families, using up to ten microsatellite markers to perform haplotype segregation analysis of the 5q31 locus. Assignment to the chromosome 5q PDS locus was excluded in one of the six North American PDS pedigrees, as chromosome 5q31 haplotypes were incompatible with linkage to this locus. The remaining five PDS pedigrees showed haplotype segregation consistent with linkage to 5q31, generating a maximum combined lod score of 1.87 (theta=0) at marker D5S2011. In this study, we establish genetic heterogeneity for PDS, catalog 21 genes within the originally defined PDS interval, and identify additional recombinations that indicate a higher priority interval, containing just 11 genes.

Chromosome Disorders↗
PubMed1992

Partial purification of serum prostacyclin stimulatory activity by heparin-agarose column; abnormality detected in diabetics.

Human plasma-derived serum (PDS) stimulated the production of 6-keto-PGF1 alpha (a stable metabolite of PGI2) by cultured bovine aortic endothelial cells. The stimulation was both time- and dose-dependent. The main prostacyclin stimulatory activity (PSA) in human PDS remained biologically active after dialysis and was inhibited by the simultaneous addition of heparin. The maximum inhibition of PSA was obtained with 10 micrograms/ml heparin. PDS obtained from patients with non-insulin-dependent diabetes mellitus (NIDDM, n = 24) showed significantly less PSA than that from the control subjects (n = 11). A decrease in PSA was also found in diabetic patients using dialyzed PDS. The PSA in human PDS had a specific binding affinity to heparin-agarose and the bound PSA was eluted by a linear gradient of NaCl, which showed two major PSA peaks at 1.0 and 1.5 M NaCl. The dialyzed, mixed PDS from patients with NIDDM and the control subjects was independently applied to a heparin-agarose column and eluted by a linear gradient of NaCl. Comparing the PSA in each peak between the diabetic and the control dialyzed PDS, the PSA at 1.5 M NaCl was markedly decreased in the diabetic patients, but the PSA at 1.0 M NaCl did not change significantly. These observations suggest that the decreased PSA in human diabetic PDS may result mainly from the decrease in the activity of a specific non-dialyzed factor(s) which can bind to heparin. The decreased PSA in serum seems to be responsible in part for decreased PGI2 synthesis by the vascular wall of diabetics.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Inhibitory mechanisms terminating paroxysmal depolarization shifts in hippocampal neurons of rats.

The mechanisms responsible for the termination of paroxysmal depolarization shifts (PDS) were studied with intracellular recordings on CA1 neurons of rat hippocampal slices. Epileptiform activity was induced by application of penicillin, bicuculline or Mg-free artificial cerebrospinal fluid (ACSF). PDS in penicillin-containing and Mg-free ACSF were markedly prolonged when GABAA-dependent IPSPs were blocked by bicuculline. PDS in bicuculline-containing ACSF were furthermore prolonged after block of potential dependent K+ conductances by TEA. TEA also exerted some effect on PDS induced by penicillin containing or Mg-free ACSF. Block of GABAB-dependent IPSPs or Ca(2+)-dependent K+ currents did not affect PDS duration in any of the three models. It is concluded that PDS termination is due to active inhibitory processes which comprise different components. If one of these components is blocked another inhibitory component governs PDS repolarization resulting in PDS with a slightly different duration but otherwise unchanged features.

Animals↗
PubMedDate not supplied

Co-occurrence of DSM-IV personality disorders in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions.

The objective of this study was to determine the co-occurrence of 7 of the 10 Diagnosis and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision ( DSM-IV-TR ) personality disorders (PDs) in the US population. Face-to-face interviews were conducted with 43 093 respondents in the National Institute on Alcohol Abuse and Alcoholism's 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative survey of the US population. Odds ratios were calculated to determine associations among PDs. All associations among PDs were positive and statistically significant. PDs were significantly associated with other PDs within the same cluster, in addition to being highly associated with PDs of other DSM-IV PD clusters. Co-occurrence between DSM-IV PDs is pervasive in the US general population. Future research is needed on the creation of dimensional representations of DSM-IV PDs as an adjunct to categorical diagnoses.

Adolescent↗
PubMed2003

Value of power doppler and 3D vascular sonography as a method for diagnosis and staging of prostate cancer.

OBJECTIVES: To compare the value of Power Doppler Sonography (PDS) and B mode sonography in the diagnosis of prostate cancer and to assess the value of PDS to specify capsular effraction of the cancer. PATIENTS AND METHODS: 323 patients were investigated: 41 control subjects allowed the establishment of normal vascular semiology and 282 patients with suspected cancer (PSA >4ng/ml). Power Doppler Sonography with 3D reconstruction was used to describe Power Doppler Sonography features of normal or abnormal vessels. Three types of blood supply(a: regular avascular posterior peripheral margin, b: irregular avascular posterior peripheral margin, c: vessels crossing the posterior peripheral margin) were described as a function of the presumed stage of cancer (a: intraprostatic, b: undetermined, c: extraprostatic). Comparison with histology was performed on random biopsies without Doppler (282 cases) (median PSA level = 15.8ng/ml), on second biopsies indicated with PDS (72 cases), and radical prostatectomy specimens (63 cases). RESULTS: A cancer was diagnosed in 157 of the 282 patients (55.7%) with suspected cancer. The overall sensitivity of PDS in the initial diagnosis of prostatic cancer was 92.4% and its specificity was 72% (versus 87.9% and 57.6% for sonography alone respectively). The negative predictive value of PDS was elevated to 80.6% (p<0.0001). Targeting area presenting abnormal blood flow in any part of the prostate was useful to detect isoechoic or lesions in patients with first negative biopsy results (in 41 of 72 targeted patients with first negative biopsies with PDS a cancer was diagnosed: 58% of these cancers had less than 3 positive biopsies and 34% only one positive biopsy). The 3 vascular types a, b, c were evaluated prospectively in the detection of capsular effraction. The presence or absence of vessels crossing the capsule to determine an extracapsular extension was a significant sign (p<0.0001). Capsular effraction was detected in 3 of the 27 cases (11%) of type a cancer and in 16 of the 18 cases (87%) of type c cancer. CONCLUSION: PDS improves the accuracy of echographic imaging in the diagnosis of cancer. Combining first sextant biopsies and targeted areas presenting abnormal blood flow using PDS can increase cancer detection with an optimized number of biopsy cores. The risk of extracapsular involvement can be evaluated by the presence of vessels perforating the capsule.

Aged↗
PubMed1996

A perspective on radiology residency curriculum guidelines: results of the 1995 survey of program directors.

RATIONALE AND OBJECTIVES: The development of curriculum guidelines for radiology residency has been found to be favored by 80% of program directors (PDs) nationwide. I surveyed PDs to develop a consensus of opinion concerning minimum training requirements in the subspecialty rotations. METHODS: A survey developed by members of the Ad Hoc Curriculum Committee of the Association of Program Directors in Radiology was mailed to all U.S. PDs. RESULTS: One hundred forty-one (82%) completed responses were received. There was agreement among the PDs about the minimum length of training needed in the various subspecialties. Seventy-four percent of the PDs supported the concept of developing educational objectives and goals in each subspecialty and of specifying procedures in which residents should be trained. Only a minority of PDs thought that the training guidelines should specify minimum numbers of procedures. CONCLUSION: The consensus of PDs is that the radiology residency curriculum should include a minimum of 3 months in each of the following categories: chest radiology, gastrointestinal radiology, musculoskeletal radiology, pediatric radiology, cardiovascular and interventional radiology, sonography, and body computed tomography (CT) scanning. In neuroradiology, inclusive of neuroangiography, neuro CT scanning, and neuro magnetic resonance (MR) imaging, a resident should spend 4 months. At least 2 months should be devoted to each of the following: uroradiology, mammography, body MR imaging, and emergency radiology. A majority of PDs also favored developing educational objectives for each of the subspecialty rotations.

Curriculum↗
PubMed2002

Distribution of rod- and cone-specific phosducins in retinas of non-mammalian vertebrates.

In mammalian retinas, it has been believed that just one kind of phosducin (PD) commonly exists in both rods and cones. However, we have previously reported that there are rod- and cone-specific PDs (OlPD-R and OlPD-C) in medaka (Oryzias latipes) retina [FEBS Lett., 502, 117-121, 2001]. To clarify the distribution and evolution of these photoreceptor type-specific PDs, we investigated PDs of another teleost and a reptile. Immunohistochemical and Western blot analyses using anti-medaka PD antisera demonstrated that two kinds of PDs are expressed in zebrafish (Danio rerio) photoreceptor cells. Our study is suggestive that teleosts generally possess rod- and cone-specific PDs. We isolated a cDNA encoding putative PD (PmlPD) of a diurnal gecko (Phelsuma madagascariensis longinsulae). Because diurnal gecko possesses a pure-cone retina, it was expected that PmlPD would be expressed in cones. Molecular phylogenetic analysis demonstrated that PmlPD was more closely related to mammalian PDs than teleost cone-specific PDs, suggesting that the rod- and cone-specific subtype of teleost PDs have arisen after the teleost-tetrapod divergence.

Amino Acid Sequence↗
PubMed2004

Alkaline side-coordination strategy for the design of nickel(II) and nickel(III) bis(1,2-diselenolene) complex based materials.

The deprotonated form of the pyrazine-2,3-diselenol (pds) ligand, pds(2-), reacts with Ni(II) inorganic salts to form the nickel compounds [Ni(II)(pds)(2)](nBu(4)N)(2) (1), [Ni(II)(pds)(2)]Na(2).2H(2)O (2), and [Ni(III)(pds)(2)](2)Na(2).4H(2)O (3), depending on the reaction conditions. They are characterized by NMR, EPR, UV-vis, and IR spectroscopies, elemental analysis, cyclic voltammetry, and X-ray crystallography. The crystal structure of compound 3 shows the formation of segregated stacks of Ni(pds)(2-) units, with a strong dimerization along the stacks. The stacked fashion of the crystal packing was expected since the supramolecular forces of the alkaline side coordination to the pyrazine moieties dominate, as happens in the recently reported analogous copper system [Cu(III)(pds)(2)]Na.2H(2)O. The structure of 2 further emphasizes the alkaline coordination as the dominating supramolecular event, and an orthogonal array of 2D layers is observed. The absence of alkaline cations in complex 1 is reflected in a crystal packing with isolated complex Ni(pds)(2)(2-) units. The dimerization found in the paramagnetic Ni(III) complex 3 promotes a very strong antiferromagnetic interaction, leading to a singlet ground state.

Journal Article↗
PubMed2006

Oxidative stress during peritoneal dialysis: implications in functional and structural changes in the membrane.

Progressive peritoneal fibrosis, membrane hyperpermeability, and ultrafiltration failure have been observed in patients on long-term peritoneal dialysis (PD). The present study tested the hypothesis that reactive oxygen species (ROS) generated by conventional PD solution (PDS) mediate functional and structural alterations of peritoneal membrane in vivo. Sprague-Dawley rats were randomized to control, PDS, PDS with an antioxidant, and PDS with an angiotensin II (Ang II) receptor blocker. Commercial PDS containing 3.86% glucose (20-30 ml) with or without N-acetylcystein (NAC) 10 mM or losartan 5 mg/kg was administered intraperitoneally twice a day for 12 weeks. Control rats received sham injection. Rats treated with PDS had significantly lower drain volume and D(4)/D(0) glucose, but higher D(4)/P(4) creatinine and increased membrane thickness and endothelial NOS (eNOS) expression compared to control rats. Omental transforming growth factor (TGF)-beta1, vascular endothelial growth factor (VEGF), collagen I, and heat-shock protein (hsp) 47 expression and lipid peroxide levels and dialysate VEGF and Ang II concentrations were significantly increased in rats treated with PDS compared to control. All of these changes were prevented by both NAC and losartan. In conclusion, the present study demonstrates that ROS generated by conventional PDS are, in large part, responsible for peritoneal fibrosis and membrane hyperpermeability. We suggest that antioxidants or Ang II receptor blockers may allow better preservation of the structural and functional integrity of the peritoneal membrane during long-term PD.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2002

Relevance of basic laboratory and clinical research activities as part of the vascular surgery fellowship: an assessment by program directors and postfellowship surgeons.

INTRODUCTION: Decreased federal monies for graduate medical education, increased clinical training demands, and a decreased pool of general surgery trainees applying to vascular surgery fellowships have brought into question the relevance of the fellowship research experience. This study sought to describe the recent laboratory experience of the fellows, the value of this experience to program directors (PDs) and the trainees, and what factors related to this experience contributed to the trainee entering an academic career versus a private practice career. METHODS: A survey regarding the relevance of research experience during fellowship training was mailed in 2001 to all Accreditation Council for Graduate Medical Education-approved vascular surgery fellowship PDs and vascular surgery fellows (VSFs) from 1988 to 2000 applying for the American Board of Surgery Certificate of Added Qualification in General Vascular Surgery. RESULTS: Survey responses were received from 89% of the PDs (74/83) and 69% of the VSFs (259/378). Among the PDs, 70% had completed an approved fellowship, and current bench research was performed by 46%. The PDs afforded protected research time to 69% of the VSFs (with a mean duration of 12 months). This research was in the basic science laboratory 34% of the time. Only 42% of the PDs considered basic laboratory research to be an important part of the fellowship, whereas 99% believed that clinical research was important. Among the PDs, 42% believed that more practice-oriented fellowships with no basic research were needed, whereas 35% believed that basic research should remain an integral component of the fellowship. VSF basic science productivity was significantly greater from those programs that offered protected research time as compared with those that did not (mean basic science paper published, 1.7 +/- 0.1 versus 0.3 +/- 0.6 per VSF; P <.001). At the time of the survey, 99 VSFs had entered academic careers and 136 were in private practice. Basic science research had been undertaken by 56% of the VSFs during medical school and by 53% during general surgery residency. Research during the fellowship was performed by 65% of the VSFs. This experience was considered helpful in choosing an academic or private practice career by 44% of the VSFs. A greater proportion of academic surgeons had research experience as VSFs when compared with VSFs who became private practitioners (71% versus 57%; P <.05). VSFs who entered academic careers had a more productive publication record in fellowship than did those who chose private practice (mean paper, 2.4 versus 1.5; P <.05). Overall, 78% of the VSFs believed that their research experience was maturing beyond the technical skills learned. CONCLUSION: This report provides a benchmark of the vascular surgery fellowship research experience. Most VSFs considered the research experience as it now exists to be worthwhile, and less than half of the PDs believed that it should remain as it is. Research experience in fellowship seemed more influential than that in medical school or general surgical residency in promoting an academic career.

Biomedical Research↗
PubMed2001

Surveillance of nosocomial infections in ICUs: is postdischarge surveillance indispensable?

OBJECTIVE: To determine how many infections are missed if the postdischarge surveillance (PDS) follow-up of intensive care unit (ICU) patients that is required by the National Nosocomial Infection Surveillance System method is not done. DESIGN: ICU patients were followed up and surveillance results with PDS (gold standard) and without PDS were compared. SETTING: Surgical or interdisciplinary ICUs in eight German acute-care hospitals. PATIENTS: All 1,857 patients within a 6-month period in the participating ICUs (a total of 9,129 ICU-patient-days). RESULTS: Without PDS, 45 urinary tract infections (UTIs) were diagnosed, compared with 53 with PDS; thus, 15% of the UTIs were missed if no postdischarge follow-up was performed. Three nosocomial pneumonias (4%) and one bloodstream infection (8%) also were missed if surveillance was carried out without PDS. A total of 198 nosocomial infections (NIs) were recorded with PDS, compared to 175 NIs without PDS. Approximately 12% of all ICU-associated NIs were missed if no follow-up was done. CONCLUSIONS: Since it is very time-consuming to follow patients after their transfer from the ICU, we do not perform a postdischarge follow-up of patients in the course of routine surveillance.

Cross Infection↗
PubMed2005

Energy cost and cardiorespiratory adaptation in the "Get-Up-and-Go" test in frail elderly women with postural abnormalities and in controls.

BACKGROUND: This study investigated the hypothesis that postural abnormalities might increase energy expenditure during a clinical functional test in frail elderly persons. METHODS: Two groups of hospitalized women (aged 73 to 100 years) were recruited. Women who showed postural and gait abnormalities as described in the psychomotor disadaptation syndrome (PDS) were compared with control participants. The authors measured energy expenditure during the timed "up and go" test. For each participant, oxygen uptake, carbon dioxide output, expiratory minute ventilation, breathing frequency, heart rate, and alveolar ventilation were recorded 10 minutes before, during, and 10 minutes after exercise. The arterial pressure of carbon dioxide was estimated from expired gases. RESULTS: The mean oxygen uptake values were significantly higher in women with PDS than in the control group during exercise and recovery periods (4.89 +/- 1.68 vs 3.75 +/- 1.25 ml . kg(-1) . min(-1) and 4.69 +/- 1.45 vs 3.76 +/- 0.97 ml . kg(-1) . min(-1), respectively [p <.05]). Expiratory minute ventilation was always higher in women with PDS than in controls regardless of the period of the test (p <.05), and alveolar ventilation was higher in women with PDS only during the exercise period (p <.05). The estimated arterial pressure of carbon dioxide did not change significantly between the different phases of the test but was always lower (p <.05) in women with PDS compared with the control group. CONCLUSIONS: The significant increase in oxygen uptake during the exercise and recovery periods in women with PDS compared with controls suggests that postural abnormalities that characterize PDS may be associated with an increase in energy expenditure. In clinical practice, the low capacity to tolerate even moderate exercise must be considered when specific rehabilitation programs are offered to women with PDS.

Adaptation, Physiological↗
PubMed1996

Personality disorders and treatment outcome in methadone maintenance patients.

This study examined the relationship between personality disorder (PDs) and 7-month treatment outcome in 197 men admitted to methadone maintenance. Subjects reported pervasive improvement, and the amount of improvement did not significantly differ for those subjects with and without PDs. PD subjects entered treatment with more severe self-reported drug, alcohol, psychiatric, and legal problems, and despite progress, remained more problematic in those areas relative to subjects without PDs. Subjects with antisocial PD had admission and 7-month problem status similar to subjects with other PDs. The 7-month urinalysis results for opiates and cocaine showed no significant differences between subjects with and without PDs. Fewer PD subjects stayed in treatment continuously for the 7-month period. Several cluster B PDs-borderline, antisocial, and histrionic-predicted poorest overall outcomes. Methadone-maintained patients with PDs may warrant additional treatment services if they are to approach the functional level of patients without PDs.

Adult↗
PubMed1998

Initiation and maintenance of virus-induced gene silencing

The phytoene desaturase (PDS) gene of Nicotiana benthamiana was silenced in plants infected with potato virus X (PVX) vectors carrying PDS inserts, and a green fluorescent protein (GFP) transgene was silenced in plants infected with PVX-GFP. This virus-induced gene silencing (VIGS) is post-transcriptional and cytoplasmic because it is targeted against exons rather than introns of PDS RNA and against viral RNAs. Although PDS and GFP RNAs are most likely targeted through the same mechanism, the VIGS phenotypes differed in two respects. PDS mRNA was targeted by VIGS in all green tissue of the PVX-PDS-infected plant, whereas PVX-PDS was not affected. In contrast, VIGS of the GFP was targeted against PVX-GFP. Initially, VIGS of the GFP was initiated in all green tissues, as occurred with PDS VIGS. However, after 30 days of infection, the GFP VIGS was no longer initiated in newly emerging leaves, although it was maintained in tissue in which it had already been initiated. Based on these analyses, we propose a model for VIGS in which the initiation of VIGS is dependent on the virus and maintenance of it is virus independent.

Journal Article↗
PubMed2003

Emergency medicine residency training in electrocardiogram interpretation.

OBJECTIVES: A national survey of emergency medicine (EM) residency program directors (PDs) was conducted to review training and evaluation of residents in electrocardiogram (ECG) interpretation and to assess the attitudes of PDs toward establishing national criteria for ECG competency. METHODS: An eight-question multiple-part survey was mailed to all 122 EM PDs. The presence of a formal ECG curriculum, teaching formats, and methods to assess competency were queried. The PDs' opinions on developing a national ECG curriculum, standardized assessment tool, and competency requirement for graduation were solicited on a five-point Likert scale. RESULTS: Surveys were received from 87 (71.3%) of the 122 EM residency programs. Of the responding programs, 56 (64.4%) had a formal ECG curriculum. Only 18 (20.7%) programs stated that they test for ECG competency, and even fewer, ten (11.5%) programs, require that residents prove competency to graduate. Although 32 (48.3%) PDs endorsed the idea of a national ECG curriculum, 51 (58.6%) opposed the implementation of a national ECG examination for EM. Similarly, 50 (57.5%) PDs opposed a national ECG competency requirement for graduation. CONCLUSIONS: While a majority of EM residency programs surveyed have a formal curriculum for ECG interpretation, less than a fourth formally test their residents or require proof of competency. The majority of residency PDs oppose the development of a national ECG examination or competency requirement for graduation. Implementation of the Accreditation Council for Graduate Medical Education directive for the demonstration of clinical competencies will be challenging given the current position of PDs.

Adult↗