Physiological and Psychological Effects of Delivering Medical News Using a Simulated Physician–Patient Scenario

We examined the acute stress response associated with having to deliver either bad or good medical news using a simulated physician–patient scenario. Twenty-five healthy medical students were randomly assigned to a bad medical news (BN), a good medical news (GN), or a control group that read magazines during the session. Self-report measures were obtained before and after the task. Blood pressure and heart rate were measured throughout the task period. Four blood samples were obtained across the task period. The BN and GN tasks produced significant increases in self-reported distress and cardiovascular responses compared with the control group. There was also a significant increase in natural killer cell function 10 min into the task in the BN group compared with the control group. The BN task was also somewhat more stressful than the GN task, as shown by the self-report and cardiovascular data. These findings suggest that a simulated physician–patient scenario produces an acute stress response in the physician, with the delivery of bad medical news more stressful than the delivery of good medical news.     

Interlaboratory validation of a CD71-based flow cytometric method (Microflow) for the scoring of micronucleated reticulocytes in mouse peripheral blood

An interlaboratory study was performed to validate an anti-CD71/flow cytometry-based technique for enumerating micronucleated reticulocytes (MN-RETs) in mouse peripheral blood. These experiments were designed to address International Workshop on Genotoxicity Test Procedures validation criteria by evaluating the degree of correspondence between MN-RET measurements generated by flow cytometry (FCM) with those obtained using traditional microscopy-based methods. In addition to these cross-methods data, flow cytometric MN-RET measurements for each blood sample were performed at two separate sites in order to evaluate the reproducibility of data between laboratories. In these studies, groups of male CD-1 mice were treated with vehicle (saline or vegetable oil), a negative control (saline or vegetable oil), or four dose levels of five known genotoxicants (clastogens: cyclophosphamide, benzo[a]pyrene, 5-fluorouracil, methotrexate; aneugen: vincristine sulfate). Exposure occurred on 3 consecutive days via intraperitoneal injection, and blood samples were obtained approximately 24 hr after the final treatment. MN-RET frequencies were determined for each sample based on the analysis of 2,000 (microscopy) and 20,000 (FCM) reticulocytes. Regardless of the method utilized, each genotoxic agent was observed to cause statistically significant increases in the frequency of MN-RETs, and each response occurred in a dose-dependent manner. Spearman's correlation coefficient (rs) for FCM versus microscopy-based MN-RET measurements (nine experiments, 252 paired measurements) was 0.740, indicating a high degree of correspondence between methods. The rs value for all flow cytometric MN-RET measurements performed at the two independent sites was 0.857 (n = 248), suggesting that the automated method is highly transferable between laboratories. Additionally, the flow cytometric system offered advantages relative to microscopy-based scoring, including a greater number of cells analyzed, much faster analysis times, and a greater degree of objectivity. Collectively, data presented in this report suggest that the overall performance of mouse peripheral blood micronucleus tests is enhanced by the use of the flow cytometric scoring procedure.     

pH modulates conducting and gating behaviour of single calcium release channels

Intracellular pH changes affect excitation-contraction coupling in skeletal, and cardiac muscles. However the proton implication in modulating the sarcoplasmic reticulum Ca²⁺ release channel activity has never been visualized at single channel level. A large conducting Ca²⁺ release pathway has previously been characterized after incorporation of skeletal and cardiac sarcoplasmic reticulum vesicles into planar lipid bilayers. This channel has been activated by micromolar and millimolar concentrations of Ca²⁺ and ATP, respectively. The pH was independently varied on each side of the channels. Acidification of the cis-chamber (7.4 to 6.6) induced a modification of the gating behaviour, resulting in a decrease of the open probability. This effect was completely reversible. On the other hand, acidification of the trans-chamber (7.4 to 6.8) induced a reduction of the unitary conductance of the sarcoplasmic reticulum Ca²⁺ release channel.     

Pediatric circulatory support systems

Ventricular assist devices (VADs) are a valid option for long term circulatory support in pediatric patients with postoperative myocardial failure or debilitating heart defects. Most clinical experience to date has involved the short-term support of patients weighing 6 kg and larger. For cases of VAD implementation in pediatric patients, the assist device showed tremendous promise in reversing cardiac failure and providing adequate support as a bridge to cardiac transplantation. The Medos-HIA system, Berlin Heart, Medtronic Bio-Medicus Pump, Abiomed BVS 5000, Toyobo-Zeon pumps, and Hemopumps have proven successful for short-term circulatory support for the pediatric population. The Jarvik 2000 and Pierce-Donachy pediatric system further demonstrate the potential to be used for pediatric circulatory support. The clinical and experimental success of these support systems provide encouragement to believe that long-term support is possible.     

A phase II trial of temozolomide and IFN-alpha in patients with advanced renal cell carcinoma.

The combination of temozolomide (TEM) and interferon-alpha (IFN-alpha) previously demonstrated a 30% response rate in metastatic melanoma. A single institution, phase II trial evaluating the efficacy of TEM/IFN in patients with advanced renal cell carcinoma (RCC) was conducted. Safety and tumor response were the main outcomes. Eligible patients received 200 mg/m(2)/day TEM orally on days 1-5 every 28 days, with IFN 2.5 million U/m(2)/day subcutaneously (s.c.) three alternate days/week for days 1-15 first cycle, then 5 million U/m(2)/day s.c. 3 alternate days/week throughout each 28-day cycle. Efficacy was evaluated every 8 weeks, and dose-limiting toxicities (DLTs) were treated with dose reductions of the culprit drug. Sixteen patients (ages 37-67) were initially enrolled. Of the 14 evaluable patients, there was one minor response. Best response was stable disease, with 7 patients remaining on study for > or =6 months. Five were alive for more than 2 years, and 2 remain alive at 45 and 50 months after enrollment. DLTs included TEM-induced myelosuppression and IFN-induced fever/chills. Other toxicities were mild to moderate (grades 1-3). The combination of TEM/IFN proved quite tolerable. This regimen appears inactive in terms of response in this population with poor prognosis, but the patients with stable disease > or =6 months remain of interest.     

Does fish oil supplementation in pregnancy reduce the risk of allergic disease in infants?

PURPOSE OF REVIEW: Parallel increases in many inflammatory diseases over the last 40 years suggest that common environmental changes are promoting inflammatory immune responses and/or inhibiting the processes that normally keep these in check. One key change during this period has been declining intakes of anti-inflammatory dietary factors, including omega-3 polyunsaturated fatty acids (n-3 PUFA). As allergic diseases often first manifest in early infancy, prevention strategies need to be targeted early, even in utero. This review will examine recent evidence for the use of fish oil during this early period as a primary prevention strategy for allergic disease. RECENT FINDINGS: N-3 PUFA have well documented anti-inflammatory effects in vitro and have also been demonstrated to have health benefits in a range of chronic inflammatory diseases, including cardiovascular disease, rheumatoid arthritis and diabetes, supporting their role in modulating inflammation in vivo. Although the effects of fish oil supplementation in established allergic disease are less convincing, there is accumulating evidence that dietary n-3 PUFA may have greater effects before allergic responses are established. SUMMARY: Supplementation of the maternal diet in pregnancy with n-3 PUFA may provide a non-invasive intervention with significant potential to prevent the development of allergic and possibly other immune-mediated diseases.     

Selection of strains for quality assessment of the disk induction method for detection of inducible clindamycin resistance in Staphylococci: a CLSI collaborative study

A nine-laboratory collaborative study was conducted to select positive and negative quality assessment control strains for the detection of inducible clindamycin resistance in staphylococci. Four strains of Staphylococcus aureus were tested as unknowns on 10 different days in each laboratory using the recently recommended CLSI (formerly NCCLS) disk diffusion method and the inoculum purity control method. Strains contained either macrolide-lincosamide-streptogramin B (MLSB) resistance genes encoded by erm(A) or erm(C) or a macrolide resistance efflux pump encoded by msr(A). Based upon the results of this study, strain UT 32 (now designated ATCC strain BAA-977) containing erm(A) is recommended as the positive control organism for inducible clindamycin resistance. Strain UT 25 (now designated ATCC BAA-976), which harbors the efflux pump encoded by msr(A), is recommended as the negative control organism.     

Blood Polymorphonuclear Leukocyte Activation in Atherosclerosis: Effects of Aspirin

The aim of the study was to demonstrate an activation of polymorpho-nuclear leukocytes (PMNs) in chronic progressive atherosclerosis (ATH). A group of patients with ATH, and a group of ATH patients under aspirin (ASA) therapy were compared with control persons without atherosclerotic alterations (healthy controls). Each group comprised 15 male age-matched subjects. The following inflammatory parameters related to PMN activities were measured: the polymorphonuclear leukocyte (PMN) blood count; blood PMN migration and reactive oxygen species release in vitro; the blood levels of PMN elastase, malondialdehyde, antibodies to oxidized LDL and soluble ICAM-1. In ATH patients, the PMN blood counts and the share of blood PMNs migrating upon platelet activating factor and leukotriene B4 stimulation were significnatly above the values of the healthy controls, while the other parameters were not significantly altered. ASA treatment attenuated the inflammatory response and reduced the differences between ATH and the healthy controls. It can be concluded that, in patients with chronic progressive atherosclerosis, PMNs are involved in the inflammatory process underlying the disease.     

Amplification of Ehrlichial DNA from Dogs 34 Months after Infection with Ehrlichia canis

In order to determine whether dogs in the subclinical phase of canine monocytic ehrlichiosis (CME) are carriers of Ehrlichia canis and to determine the significance of persistent indirect immunofluorescent anti-E. canis antibody titers during this phase, PCR was performed with blood, bone marrow, and splenic aspirates collected 34 months postinoculation from six clinically healthy beagle dogs experimentally infected with E. canis. At least one of the three samples (spleen, bone marrow, and blood) from four of the six dogs was PCR positive. The spleens of all four of these dogs were PCR positive, and the bone marrow and blood of two of the four dogs were PCR positive. Indirect immunofluorescent-antibody titers increased progressively during the first 5 months postinfection, remained high for an additional period of more than 11 months, and declined thereafter, suggesting that the dogs were recovering from the disease. Five of the dogs remained seropositive 34 months postinfection. The data obtained in this study demonstrate for the first time that clinically healthy dogs in the subclinical phase of CME are carriers of the rickettsia. It was shown that dogs can harbor E. canis for years without developing the chronic clinical disease and that dogs can eliminate the parasite and recover from CME without medical treatment. Our findings suggest that the spleen is the organ most likely to harbor E. canis parasites during the subclinical phase and the last organ to accommodate the parasite before elimination. It was concluded that PCR of DNA extracted from splenic aspirates is a reliable method for determining the carrier state of CME.