Structural Inequities in the Treatment of Standardized Patients and What That Means for Patient Care.

SUMMARY STATEMENT: Standardized patients (SPs) play a pivotal role in medical education. They are proxies for real patients, preparing students to meet the challenges of excellent patient care. Human simulation, with SPs, is used for teaching and assessing communication and clinical skills in medical education around the world. Standardized patients work individually with other faculty, students, or in conjunction with medical faculty to facilitate learning with feedback. In most simulation centers, SPs receive extensive training in communication and clinical skills, yet they inhabit territory often unrecognized as professional in medical education. The manner in which SPs are seen and treated by faculty and students may be a reflection of how real patients are seen and treated-not always heard, not always respected-and this tension detracts from both simulated and real patient encounters. Exploring how SPs, as proxies for real patients, are treated in medical education is a key to what we might learn and how we might close gaps in cultural respect and, ultimately, in patient care.

The welfare of growing pigs in five different production systems: assessment of feeding and housing.

Ninety-one farms were visited over a 2-year period to assess the welfare of growing pigs in five different production systems found either in France or in Spain using the Welfare Quality® protocol. This study focused on animal-based measures as indicators of 'good feeding' and 'good housing'. Multiple Generalized Linear Mixed Models were performed for each measure to evaluate the differences between production systems and to detect possible causal factors. Pigs in the conventional system presented the lowest prevalence of poor body condition, whereas extensive Mallorcan Black pigs and extensive Iberian pigs were associated with a decreased prevalence of bursitis and pig dirtiness. The straw-bedded system presented a lower prevalence of bursitis, but poorer hygiene and more susceptibility of poor body condition than the conventional system. The age of the animals had a significant effect on the appearance of bursitis in the three intensive systems studied. The type of floor was a significant causal factor of bursitis and pig dirtiness in the conventional system and among intensive Iberian pigs. The feeding system was another causal factor of pig dirtiness on more than 50% of the body in the conventional system, whereas pig dirtiness on less than 50% of the body was influenced by the age of the animals. The prevalence of huddling animals in the conventional system was associated with the highest stocking densities and the lowest environmental temperatures. The results indicate that there were important differences between production systems based on animal-based indicators of the good feeding and housing principles. The recording of the age of the animals, type of floor, feeding system, stocking density and environmental temperature can be useful to predict the appearance of a given welfare measure of 'good housing' on a farm.

Optical spectroscopy of PPV-based block copolymers of nanostructured supramolecular organic semiconductor.

The third-order nonlinearity of a PPV-based nanostructured supramolecular organic semiconductor (DBAB), with an electron donor (D) connected to an electron acceptor (A) via nonconjugated and flexible bridge (B) units, was investigated in this work at both near-resonant (532 nm) and nonresonant (1064 nm) wavelength by using degenerate four-wave mixing. The second hyperpolarizabilities of D, A, and DBAB at 532 nm were found to be approximately 2.42 x 10(-43) m2/V2, 7.75 x 10(-44) m2/V2, and 1.80 x 10(-43) m2/V2 in copolarization geometry, and approximately 1.59 x 10(-43) m2/V2, 2.59 x 10(-44) m2/V2, and 1.18 x 10(-43) m2/V2 in orthogonal polarization geometry, respectively. The second hyperpolarizabilities of DBAB at 1064 nm were approximately 1.66 x 10(-46) m2/V2 and approximately 8.77 x 10(-47) m2/V2 for parallel and orthogonal polarization cases.

Nonlinear optical properties of mushroom-shaped CdSe/CdS coreshells.

The third-order nonlinear optical susceptibilities of mushroom-shaped CdSe/CdS coreshells as a function of concentration have been investigated using polarization- and concentration-resolved degenerate four-wave mixing in a resonant region. The effective third-order nonlinear optical susceptibilities, /chi(3)xxxx/ and /chi(3)xyyx/ of CdSe/CdS coreshells were estimated to be approximately 1.86 x 10(-21)-1.03 x 10(-20) m2/V2, and approximately 0.45 x 10(-21)-6.15 x 10(-21) m2/V2, respectively, for various concentrations of approximately 0.64 x 10(-3)-4.95 x 10(-3) mol/m3. The second hyperpolarizabilities, /xxxx/ and /xyyx/, of CdSe/CdS coreshells were extracted to be approximately 2.37 x 10(-41) m5/V2 and approximately 1.29 x 10(-41) m5/V2, respectively.

Optical absorption and valence band photoemission from uncapped CdTe nanocrystals.

CdTe nanocrystals have been successfully fabricated by a mechanical alloying process. X-ray diffraction (XRD) patterns demonstrate that a single-phase CdTe compound with a zinc blende structure has been formed after ball milling elemental Cd and Te mixture powders for 27 h. The large broadening effect for the width of the {111} diffraction peak of uncapped CdTe nanocrystals on smaller size was observed in slowly scanned XRD patterns. The X-ray photoelectron spectrum was used to study the surface of the uncapped CdTe nanocrystals within both core level and valence band regions. The presence of tellurium oxide film on the surface of the uncapped CdTe nanocrystals has been detected in the X-ray photoelectron spectrum of the Te 3d core level, which was comparable to the observed amorphous oxide thin layer on the surface of uncapped CdTe nanocrystals in a high resolution transmission electron microscopy (HRTEM) image. The energy of the valence band maximum for uncapped CdTe powders blue shifts to the higher energy side with smaller particle sizes. In UV-visible optical absorption spectra of the suspension solution containing uncapped CdTe nanocrystals, the absorption peaks were locating within the ultraviolet region, which shifted toward the higher energy side with prolonged ball milling time. Both blue shifts of valence band maximum energy and absorption peaks with decreasing particle size provide a unique pathway to reveal the quantum confinement effect of uncapped CdTe nanocrystals.

Using animal data to improve prediction of human decompression risk following air-saturation dives.

To plan for any future rescue of personnel in a disabled and pressurized submarine, the US Navy needs a method for predicting risk of decompression sickness under possible scenarios for crew recovery. Such scenarios include direct ascent from compressed air exposures with risks too high for ethical human experiments. Animal data, however, with their extensive range of exposure pressures and incidence of decompression sickness, could improve prediction of high-risk human exposures. Hill equation dose-response models were fit, by using maximum likelihood, to 898 air-saturation, direct-ascent dives from humans, pigs, and rats, both individually and combined. Combining the species allowed estimation of one, more precise Hill equation exponent (steepness parameter), thus increasing the precision associated with human risk predictions. These predictions agreed more closely with the observed data at 2 ATA, compared with a current, more general, US Navy model, although the confidence limits of both models overlapped those of the data. However, the greatest benefit of adding animal data was observed after removal of the highest risk human exposures, requiring the models to extrapolate.

Primary cardiac lymphoma diagnosed by percutaneous intracardiac biopsy with combined fluoroscopic and transesophageal echocardiographic imaging.

Primary cardiac tumors have very low prevalence with cardiac lymphoma, being one of the rarest forms. Several recent reports have shown transesophageal echocardiography to be an accurate technique for characterizing and localizing these neoplasms, with results comparable to CT and MRI scans. Transvenous intracardiac tumor biopsy has been employed as a minimally invasive technique to obtain tissue samples. The addition of transesophageal echocardiographic (TEE) guidance to this process has increased the accuracy of obtaining diagnostic specimens while improving patient safety. We review published cases of this relatively new technique using combined fluoroscopic and TEE guidance and present a case of primary cardiac lymphoma diagnosed by this method. The patient achieved complete tumor remission after treatment with standard chemotherapy and remains fully functional 32 months after initial diagnosis.

Relationship between serum inositol concentration and development of retinopathy of prematurity: a prospective study.

PURPOSE: To examine the relationship between the intake of sugar inositol, serum inositol levels, and ROP in three groups of low birthweight infants receiving feedings containing various concentrations of inositol. METHODS: Infants with a birthweight <1500 g, with severe lung disease, were eligible for the study when they began enteral feedings. Infant formulas contained three different inositol concentrations: 2500, 710, and 242 micromol/L. Serum inositol concentrations were averaged over specific time intervals. A logistic regression model was used to investigate the confounding effect of duration of mechanical ventilation and oxygen therapy, birthweight, Apgar score, and serum inositol concentration on development of ROP. RESULTS: Infants receiving high inositol formula and with higher serum inositol concentrations at birth and after 30 days had a statistically significant lower incidence of severe ROP than those receiving the lower inositol formula and with lower serum concentrations (P<.05). The effective serum inositol concentration (EC90) associated with lesser disease was >215 micromol/L. By logistic regression, the odds of developing severe ROP were greater among infants with low serum inositol concentration (odds ratio=4.7, 95% confidence interval 0.90-24.8, P=.017). CONCLUSION: Inositol supplementation may help prevent the most severe form of ROP.

Displacement measurement that uses transient photoelectromotive force effects in CdTe:V with frequency-modulated lasers.

A new method of displacement measurement that uses the transient photoelectromotive force effects that arise in semiconductors illuminated by two frequency-modulated lasers is proposed and demonstrated experimentally. A height resolution of 0.85 microm was achieved experimentally; theoretical analysis charts the path toward eventual improvement of this resolution.

Donor bone marrow-derived chimeric cells present in renal transplant recipients infused with donor marrow. I. Potent regulators of recipient antidonor immune responses.

BACKGROUND: Even though a number of transplant centers have adopted donor-specific bone marrow cell (DBMC) infusions to enhance donor cell chimerism, to date there has been no direct evidence linking chimerism with tolerance induction in human organ transplant recipients. METHODS: Cells of donor phenotype were isolated 1 year postoperatively from the peripheral blood lymphocytes and iliac crest bone marrow of 11 living-related-donor (LRD) renal transplant recipients, who had received perioperative donor bone marrow cell infusions. These recipient-derived donor (RdD) cells were characterized phenotypically by flow cytometric analysis and functionally as modulators in mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML) assays. RESULTS: The yield of RdD cells ranged from 0.1 to O.9% of the starting material with the majority being TcRalphabeta, CD3 positive T cells, a substantial percentage of which coexpressed CD28. At 1 year posttransplant almost 50% of the LRD-kidney/DBMC recipients tested so far exhibited donor-specific unresponsiveness in MLR (7/17) and CML (6/13) reactions and this trend was further enhanced at 23 years. In the recipients with residual positive antidonor immune responses, the RdD cells inhibited recipient antidonor MLR and CML responses significantly more strongly than freshly isolated and similarly treated iliac crest bone marrow cells from the donor. RdD cells also inhibited the MLR of the recipient to third party allogeneic stimulator cells; however, this nonspecific effect was significantly weaker than specific inhibition. We also established long-term bone marrow cultures stimulated every 2 weeks with irradiated alogeneic feeder cells, that had similar functional properties thus possibly providing us with an in vitro correlate the RdD cells. CONCLUSIONS: These results clearly support the notion that the infused donor cells play a positive role in the induction and/or maintenance of transplant tolerance.

Effects of dopaminergic combination therapy for frontal lobe dysfunction in traumatic brain injury rehabilitation.

Traumatic brain injury poses significant and diverse challenges to rehabilitation efforts. Neurobehavioural deficits represent a particularly difficult barrier to rehabilitative progress and societal reintegration. Early studies have identified dopaminergic drugs such as amantadine, bromocriptine and sinemet as potentially assistive in countering these deficits. To date, side effect profiles have been relatively benign, noted most frequently in small-scale case trials. The case of a 40-year-old patient with bilateral frontal traumatic brain injuries, and previous arteriovenous malformation (AVM) bleed with significant ataxia, dysarthria and neurobehavioural deficits is presented. This long range study demonstrates, through multiple varied dosing schedules, a trade off between the benefits and side effects of dopaminergic therapy, with implications for a larger brain injury population.

Soluble immune mediators in POEMS syndrome with pulmonary hypertension: case report and review of the literature.

POEMS syndrome is a plasma cell dyscrasia that presents with numerous complications, one of which is rarely pulmonary hypertension. Here we present a case of POEMS syndrome with pulmonary hypertension who improved with steroids and six rounds of plasmapheresis done over 1 month, and we document the baseline immune mediator status and the changes associated with the therapeutic intervention. Serum levels of soluble immune mediators such as interleukin (IL)-5, IL-8, IL-10, and eotaxin were normal at baseline and throughout therapy, whereas those of tumor necrosis factor (TNF)-alpha, soluble TNF-receptor type I (sTNF-RI), IL-6, interferon (IFN)-gamma, IL-2, and sIL-2R, which were abnormally high at baseline normalized with steroids and plasmapheresis. Serum levels of sIL-6R, which were abnormally low at baseline, increased to normal after therapy. The latter results pinpoint not only potential mediators of the systemic manifestations of POEMS syndrome with pulmonary hypertension but also relevant markers in patient follow-up. In this respect, IL-6 has been involved in the pathogenesis of multiple myeloma and Castleman's disease, and the interplay between abnormally high levels of IL-6 and abnormally low levels of its soluble receptor, deficiencies that corrected with therapy in this patient, appears to be particularly relevant to the pathogenic manifestations of POEMS syndrome with pulmonary hypertension. These findings are discussed in the context of our current knowledge of the pathogenesis of pulmonary hypertension and of potential new therapeutic modalities for POEMS syndrome with pulmonary hypertension.

Continuing observations on the regulatory effects of donor-specific bone marrow cell infusions and chimerism in kidney transplant recipients.

BACKGROUND: Continued follow-up of a series of donor bone marrow cell (DBMC)-infused first cadaver renal transplant recipients is described (n=58), now at a 36-month actuarial time point postoperatively. Serial polymerase chain reaction-flow cytometry (PCR-Flow) and cellular immune assays of iliac crest bone marrow aspirates and peripheral blood have begun to be compared with concomitantly transplanted recipients of living-related donor (LRD) kidneys and donor marrow infusions given the same immunosuppressive regimen (n=16). There have also been comparisons (36 months) with 188 controls transplanted concomitantly, i.e., recipients of first cadaver kidney transplants, who did not receive bone marrow. METHODS: Each group was given equivalent immunosuppressive regimens of OKT3 anti-T cell induction and maintenance tacrolimus, mycophenolate mofetil, and methylprednisolone. Actuarial patient and graft survival have been 96% and 93%, respectively, in the controls and 91% and 91%, respectively, in the DBMC-infused recipients. Trough levels of tacrolimus were significantly lower in the DBMC-infused group. RESULTS: In PCR-Flow measurements, in peripheral blood up to 6 months postoperatively, there were higher levels of chimerism, i.e., in the total number of donor cells, as well as the donor CD3+ and CD34+ subsets in the LRD recipients administered DBMC infusions, compared with cadaver DBMC recipients, supporting the notion of a positive effect of histocompatibility on chimerism levels. In PCR-Flow measurements of recipient iliac crest bone marrow aspirates as in previous studies on peripheral blood, early acute rejection episodes (<1 month) were found to be associated with a later (6-14 months) decrease in donor cell lineage chimerism. However, a trend toward recovery of chimeric levels occurred by 21-28 months in a second iliac crest marrow aspirate 1 year after the first aspirate in the DBMC-infused recipients who experienced such early rejection episodes. This was in contrast to the controls in whom there were sustained low levels of iliac crest bone marrow chimerism at both the earlier and later intervals (i.e., no chimeric recovery), with 17/183 surviving controls progressing into chronic rejection. This has not yet been seen in the DBMC-infused group (0/54). In in vitro observations on cellular immune reactivity at 1 year postoperatively, decreased peripheral blood lymphocyte proliferative reactions were seen in response to phytohemagglutinin and Staph-A mitogens, as well as to cytomegalovirus and Epstein-Barr viral protein antigens in the DBMC-infused group versus the controls. Chronic immunosuppression did not seem to effect a vigorous in vitro inhibitory (regulatory) activity of bone marrow taken from these transplant recipients 2 years postoperatively in mixed lymphocyte culture and cell-mediated lympholysis reactions, using allogeneic responding cells from "normal" laboratory volunteers. Autologous peripheral blood lymphoproliferative responses to phytohemagglutinin and Staph-A mitogens, as well as to cytomegalovirus and Epstein-Barr virus protein antigens, were also regulated by either organ donor (non-immunosuppressed) bone marrow cells or by transplant recipient (immunosuppressed) bone marrow cells. What appeared to be disparate between the DBMC-infused and control groups (both immunosuppressed) was the trend for the (autologous) bone marrow suppressive effect on antiviral lymphoproliferative responses, to be stronger in the DBMC-infused group, who also had significantly (>one order of magnitude) higher levels of chimerism (P=0.01). CONCLUSIONS: It is concluded that the establishment of a chimeric state in DBMC-infused recipients, albeit of relatively low magnitude (approximately 1% at 2 years in recipient iliac crest bone marrow), has had a definite regulatory effect on immune responses. These results, therefore, add weight to the "causal" horn of the dilemma as to whether donor cell chimerism is a cause or an effect of

The effects of chimeric cells following donor bone marrow infusions as detected by PCR-flow assays in kidney transplant recipients.

40 recipients of first cadaver kidney transplants were given perioperative donor vertebral bone marrow infusions (DBMC), compared with 100 controls who did not receive donor bone marrow. The immunosuppressive regimen included OKT3, Tacrolimus, and steroid maintenance therapy, and, in some patients, newly introduced mycophenolate mofetil. This report describes the 24-mo actuarial follow-up and several immunological monitoring studies including sequential measurements of donor bone marrow lineage subset chimerism by the recently reported PCR-flow assay. This is a sensitive in situ PCR detection system for donor versus recipient histocompatibility genes as well as cell surface CD epitope markers using flow cytometry. The results indicate (a) the stabilization of the donor CD3+ and CD34+ cells in recipient peripheral blood at levels below 1% between 6 mo and 1 yr postoperatively, with a 10-fold higher level of donor cell chimerism of these lineages in recipient iliac crest marrow; (b) significantly lower levels of chimerism in peripheral blood up to 6 mo postoperatively in patients who had early acute (reversible) rejection episodes compared with those who did not; (c) a higher degree of chimerism seen in patients who were class II MHC HLA DR identical with their donors; (d) the identification of a high proportion of the donor bone marrow derived CD3 dimly staining subset of T cells (to which regulatory functions have been ascribed) in recipient peripheral blood and especially in recipient bone marrow; and (e) an unexpectedly increased susceptibility to clinically significant infections (primarily viral), and even death in the DBMC-infused group, compared with controls, but no graft losses because of rejection in the DBMC-infused group. Mixed lymphocyte culture assays showed a trend toward a greater number of nonspecifically low reactors in the DBMC group, as well as a greater number of nonspecifically high reactors in the controls (P = 0.058). The autologous mixed lymphocyte reaction also indicated a trend towards nonspecific immune activation in the DBMC group. Finally, anti-cytomegaloviral IgG antibody reactivity was significantly inhibited in the DBMC group 4-6 mo postoperatively (P = < 0.05). In the controls, there were no donor cell lineages detected by PCR-flow in the peripheral blood. These rather unexpected findings, indicating a more depressed cellular and humoral immune capacity in the DBMC cadaver kidney transplant recipients in this relatively early follow-up period, are discussed relevant to chimerism, MHC restriction, and suppressor activity brought about by specialized DBMC subsets, which still need to be defined.

Survival and neutrophil kinetics in infants with severe group B streptococcal disease treated with gamma globulin.

To estimate the efficacy of intravenous gamma globulin adjunct therapy on the course of severe neonatal group B streptococcal (GBS) disease, the hospital records of 67 confirmed cases of early-onset GBS sepsis associated with neutropenia were reviewed. Among the 33 infants who had received antibiotic agents without gamma globulin, 13 (39%) died. Among the 34 who had received antibiotic agents plus gamma globulin, 6 (18%) died (p < 0.05). Among 52 low birth weight infants, 5 (20%) of the 25 given gamma globulin died compared with 13 (48%) of the 27 not given gamma globulin (p < 0.03). Neutrophil counts rose more rapidly among survivors who received gamma globulin than among those who did not. This retrospective study suggests that intravenous gamma globulin adjunct therapy for neonatal GBS disease associated with neutropenia promotes a more rapid increase in neutrophil count and improves survival.