Ten Years' Experience Conducting the Aging Game Workshop: Was It Worth It?

In the Aging Game, medical students experience simulated physical, sensory, and cognitive deficits that are associated with disability from chronic diseases. Since 1994, the University of Minnesota has presented an innovative version of the Aging Game as part of the curriculum in a required clinical clerkship. The experiences conducting the Aging Game over the past decade were reviewed, focusing on the resources necessary to produce it and on its worth as an educational tool. Because many of the reusable props were obtained free as donations, start-up material costs were calculated at 530 dollars. Personnel necessary for each half-day presentation of the Aging Game included two faculty and a minimum of five nonfaculty serving as facilitators; a staff coordinator was also essential. Quantitative student evaluations (N=673) exhibited mean ratings of 1.41, 1.35, and 1.40 (1=excellent) for overall value, teaching effectiveness, and quality of a postsimulation discussion. Written student comments regarding the strengths of the Aging Game centered on three major themes: mode of learning, especially using role playing and simulating deficits (total of 192 comments); attitudinal change, specifically raising awareness and stimulating reflection on the experiences of disabled older adults (121 comments); and educational value, particularly the Aging Game's capacity for creating a memorable impression (56 comments). Despite consuming significant personnel resources, the Minnesota version of the Aging Game is an effective tool for stimulating long-lasting awareness and understanding of key issues related to aging and geriatrics.     

The relation of dizziness to functional decline

OBJECTIVE: to assess the effect of dizziness on the probability that an older person will die or become functionally disabled within 2 years. Dizziness is a common symptom for which the prognosis is uncertain. This report compares the prognoses for dizzy and not-dizzy older people in order to assist clinicians who diagnose and treat these patients. DESIGN: a prospective study of a representative sample of elderly (70+) non-institutionalized Americans. Elderly subjects (n = 3,798) in the Longitudinal Study of Aging (LSOA) were asked questions about the presence of dizziness, medical conditions, and functional disability in 1984. The cohort was reinterviewed about functional disability in 1986. OUTCOME MEASURE: transition from functional ability to disability after 2 years. RESULTS: Bivariate analyses showed that dizziness predicts functional decline but not mortality. Multivariate models revealed that age, race, sensory impairment, vascular disease, and other morbidity are independent predictors of becoming disabled. Controlling for these potential confounders, dizziness does not predict an increased probability of becoming disabled. CONCLUSION: Elderly people who are dizzy should be evaluated for the presence of these related conditions.     

A near-fatal reaction during granulocyte transfusion of a neonate

Although reactions to granulocyte transfusions in neonates are rarely reported, we observed a near-fatal pulmonary reaction, presumably due to white cell antibodies, in a neonate with Rh hemolytic disease. The hemolytic disease was being treated with exchange transfusions, and at 2 days after the infant's birth, bacterial sepsis was suspected and granulocyte transfusions were begun. The first granulocyte transfusion (Day 3) was uneventful. Five minutes after the beginning of the second granulocyte transfusion (Day 4), severe respiratory distress, hypotension, bradycardia, cyanosis, and acidosis suddenly occurred. The infant's serum obtained after the reaction contained granulocytotoxic and B-lymphocytotoxic antibodies that reacted with leukocytes from the second granulocyte donor. Antibodies could not be detected either in the initial infant serum or in maternal serum. However, an antileukocyte antibody was present in the serum of a parous woman donor. We used plasma from this woman to prepare reconstituted whole blood for the exchange transfusion that we performed immediately preceding the second granulocyte transfusion. Despite the sequence of events, an irrefutable cause-and-effect mechanism could not be established because the properties of the donor and neonatal antibodies were similar, but not identical. However, this catastrophic event emphasizes both the potential for adverse effects of granulocyte transfusions in neonates and the need for caution when transfusing blood from parous women.     

Recombinant human interleukin-3 stimulation of hematopoiesis in humans: loss of responsiveness with differentiation in the neutrophilic myeloid series

Recombinant human (rh) interleukin-3 (IL-3) stimulated the proliferation and differentiation of erythroid, granulocyte, macrophage, eosinophil (Eo), and mixed colonies as well as megakaryocytes from human bone marrow cells. rh IL-3 was a weaker stimulus than rh granulocyte-macrophage colony-stimulating factor (GM- CSF) for day 14 myeloid cell colonies. At day 7 of incubation, rh IL-3 stimulated a few G, M, and Eo clusters but no colonies. This loss of responsiveness of myeloid cells to rh IL-3 was accentuated with further differentiation of the cells. rh IL-3 stimulated very few or no clones after five-day incubation with enriched promyelocytes and myelocytes, whereas rh GM-CSF was an efficient stimulus. Responsiveness to rh IL-3 was completely lost in postmitotic mature neutrophils. Incubation of these cells with rh IL-3 did not result in enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) of tumor cells or superoxide anion production after stimulation with formyl-methyl-leucyl-phenylalanine (FMLP), although they could be stimulated by rh GM-CSF. In addition, preincubation of neutrophils with different concentrations of rh IL-3 failed to increase or decrease their response to rh GM-CSF. In contrast to neutrophils, mature Eos could be stimulated by rh IL-3 to kill antibody-coated tumor cells. These results show that cells of the neutrophilic myeloid series lose their responsiveness to h IL-3 as they differentiate and suggest that although h IL-3 may be an important therapeutic agent to use for hematopoietic regeneration in vivo, the lack of stimulation of mature neutrophil function makes it an unlikely sole candidate as adjunct therapy for treatment of infectious diseases.     

Catheter ablation of accessory pathways, atrioventricular nodal reentrant tachycardia, and the atrioventricular junction: final results of a prospective, multicenter clinical trial. The Atakr Multicenter Investigators Group

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of a temperature-controlled radiofrequency catheter ablation system. METHODS AND RESULTS: The patient population included 1050 patients who had undergone ablation of atrioventricular nodal reentrant tachycardia (AVNRT), an accessory pathway (AP), or the atrioventricular junction (AVJ). Ablation was successful in 996 patients. The probability of success was highest among patients who had undergone ablation of the AVJ, lowest in patients who had undergone ablation of an AP, and in between for patients who had undergone ablation of AVNRT. A major complication occurred in 32 patients. Four variables predicted ablation success (AVJ, AVNRT, or left free wall AP ablation and an experienced center). Four factors predicted arrhythmia recurrence (right free wall, posteroseptal, septal, and multiple APs). Two variables predicted development of a complication (structural heart disease and the presence of multiple targets), and 3 variables predicted an increased risk of death (heart disease, lower ejection fraction, and AVJ ablation). CONCLUSIONS: These findings may serve as a guide to clinicians considering therapeutic options in patients who are candidates for ablation.     

卡马西平对癫痫患者染色体畸变率和姐妹染色单体交换频率的影响及与叶酸的

目的 研究卡马西平（ＣＢＺ）的诱变性及其与叶酸的关系,探讨ＣＢＺ致畸及叶酸防止致畸的机制。方法 应用细胞遗传学方法,检测１５例单服ＣＢＺ及１５例ＣＢＺ加叶酸的癫痫患者外周血淋巴细胞染色体畸变率（ＣＡＲ）、姐妹染色单体交换（ＳＣＥ）频率,同时用放免法测定血清叶酸含量,并与未服药癫痫对照组及正常对照组进行比较。结果 单服ＣＢＺ组患者的ＣＡＲ和ＳＣＥ频率较对照组增高,其血清叶酸含量较正常对照组下降;单服ＣＢＺ组患者的ＣＡＲ和ＳＣＥ频率较服ＣＢＺ加叶酸组增高;ＣＢＺ血药浓度与叶酸水平ＣＡＲ及ＳＣＥ之间未发现明显相关性。结论 ＣＢＺ具有ＤＮＡ损伤效应,其损伤效应可能与ＣＢＺ干扰叶酸代谢有关,补充叶酸可以有效防止ＣＢＺ引起的ＤＮＡ损伤。     

Oesophageal adenocarcinoma is associated with a deregulation in the MYC/MAX/MAD network

Oesophageal adenocarcinoma, which arises from an acquired columnar lesion, Barrett's metaplasia, is rising in incidence more rapidly than any other cancer in the Western world. Elevated expression of c-MYC has been demonstrated in oesophageal adenocarcinoma; however, the expression of other members of the MYC/MAX/MAD network has not been addressed. The aims of this work were to characterise the expression of c-MYC, MAX and the MAD family in adenocarcinoma development and assess the effects of overexpression on cellular behaviour. mRNA expression in samples of Barrett's metaplasia and oesophageal adenocarcinoma were examined by qRT-PCR. Semi-quantitative immunohistochemistry and western blotting were used to examine cellular localisation and protein levels. Cellular proliferation and mRNA expression were determined in SEG1 cells overexpressing c-MYCER or MAD1 using a bromodeoxyuridine assay and qRT-PCR, respectively. Consistent with previous work expression of c-MYC was deregulated in oesophageal adenocarcinoma. Paradoxically, increased expression of putative c-MYC antagonists MAD1 and MXI1 was observed in tumour specimens. Overexpression of c-MYC and MAD proteins in SEG1 cells resulted in differential expression of MYC/MAX/MAD network members and reciprocal changes in proliferation. In conclusion, the expression patterns of c-MYC, MAX and the MAD family were shown to be deregulated in the oesophageal cancer model.