Chimeric bispecific OC/TR monoclonal antibody mediates lysis of tumor cells expressing the folate-binding protein (MOv18) and displays decreased immunogenicity in patients

The current environment in which medicine is taught and practiced requires that medical schools pay increased attention to the faculty member's roles, rewards, career development, and productivity. Medical schools must make strategic decisions about the allocation of resources that can nurture their faculties and support the activities in academic and community settings in which faculty are involved. From 1993 to 1995 Allegheny University of the Health Sciences (formerly Medical College of Pennsylvania and Hahnemann University) designed a comprehensive system for the professional development of faculty. This system is based upon expanded categories of faculty academic activity and scholarship. New programs were implemented to reorient faculty toward conducting and documenting the expanded array of scholarly activities. The main characteristics of the new system are the establishment of formally defined performance expectations, the vertical alignment of the individual faculty member's objectives with the department's mission and the school's mission, and an increasing emphasis upon faculty interdependence, accountability, and use of sound business practices. The authors describe these and other aspects of the design of the new system in detail and report initial results and lessons learned from the system's implementation, evaluation, and dissemination throughout the university. The long-term success of this comprehensive professional development program will be assessed over time by observing how this institution advances its mission in a well-planned and cost-effective manner that retains talented, productive, and professionally fulfilled faculty.     

Outcome of blunt thoracic aortic injury in a level I trauma center: an 8-year review

BACKGROUND: The purpose of this study was to evaluate our experience with blunt thoracic aortic injury and identify factors predictive of outcome. METHODS: Hospital charts, trauma registry data, and autopsies of 64 patients with blunt thoracic aortic injury from 1988 to 1995 were reviewed. RESULTS: Patients were identified and segregated based on admission physiology. Group 1 patients (n = 19) arrived in arrest. Group 2 patients (n = 10) arrived in shock with systolic BP 90. Group 3 patients (n = 35) arrived with systolic BP>90. All patients in groups 1 and 2 expired. Injury Severity Scores for nonsurvivors in group 3 (n = 12) were significantly higher than survivors. There were no significant differences when comparing time of injury to repair or arrival between groups, or in mortality or paralysis comparing repair techniques or clamp/bypass times. Double lumen endotracheal tubes caused significant operative delays compared to single lumen tubes. CONCLUSIONS: Predictors of survivability were hemodynamic stability on arrival and lower Injury Severity Scores. In thoracic aortic injury patients arriving hemodynamically stable, Injury Severity Score correlated with mortality but not paralysis.     

Anti-D in a D-positive renal transplant patient

PURPOSE: We report a case of postoperative reparalysis in the recovery room, following nebulized epinephrine. The patient was pharmacologically reversed with edrophonium after paralysis with rocuronium. CLINICAL FINDINGS: A 12-yr-old girl developed postoperative reparalysis following the intraoperative administration of rocuronium. A total of 0.92 mg.kg-1 rocuronium was administered. After surgery, pharmacological reversal was achieved with 20 mg edrophonium with 0.15 mg atropine sulfate iv 35 min after the last administration of rocuronium. Muscular relaxation was monitored using an ulnar peripheral nerve stimulator (PNS). After reversal, a full train-of-four and sustained tetanus at 50 Hz were present. In the recovery room, following nebulized epinephrine, the patient became apneic. The patient was paralyzed and an ulnar PNS demonstrated only one faint twitch. The paralysis was reversed with 1.5 mg neostigmine with 0.3 mg glycopyrrolate. CONCLUSION: Postoperative reparalysis following rocuronium may be a cause of postoperative respiratory distress. The definitive diagnosis is made using PNS and observing the response to pharmacological reversal. Nebulized epinephrine may have a previously undescribed role in the development of postoperative reparalysis.     

Akathisia in adults with mental retardation: development of the Akathisia Ratings of Movement Scale (ARMS)

We developed an akathisia rating scale for use with persons who have mental retardation and screened for the occurrence of akathisia in three samples: 66 adults receiving maintenance neuroleptic treatment, 20 adults not receiving neuroleptics, and 8 adults undergoing neuroleptic dose reduction. The scale had an acceptable level of interrater reliability and validly measured group differences related to neuroleptic treatment status. Using an empirically derived cut-off-score, we estimated the prevalence rate for akathisia to be 5% in neuroleptic-free subjects, 17% in neuroleptic-maintenance subjects, and 25% in neuroleptic-reduction subjects. Akathisia, dyskinesia, and stereotypy manifested as qualitatively different movement topograhies. The occurrence of dyskinesia stereotyped movement disorder was associated significantly with an increased occurrence of akathisia.     

Early surgery in patients with mitral regurgitation due to flail leaflets: a long-term outcome study

BACKGROUND: The optimal timing for surgery in patients with mitral regurgitation is disputed. Because of the frequency of left ventricular dysfunction, which is difficult to predict, early surgery has been recommended, but its potential benefits have not been demonstrated. METHODS AND RESULTS: The outcomes of 221 patients (mean age, 65 +/- 13 years; 71% males) with flail leaflets diagnosed with two-dimensional echocardiography between 1980 and 1989 who were eligible for operation were analyzed. Group I comprised 63 patients who had early mitral valve surgery (within 1 month after diagnosis). Group II comprised 158 patients initially treated conservatively (80 of whom were operated on later). Group I patients were younger (P=.009), had more symptoms (P<.0001), and were more frequently in atrial fibrillation (P=.023) than group II patients. There was no difference in ejection fraction between the groups. The early surgery strategy was followed by an improved overall survival rate (P=.028) and a lower incidence of cardiovascular deaths (P=.025), congestive heart failure (P=.046), and new chronic atrial fibrillation (P=.032), as confirmed by multivariate analysis (adjusted risk ratios of 0.31, 0.18, 0.38, and 0.05, respectively; all P<.02). CONCLUSIONS: In patients with mitral regurgitation due to flail leaflets, the strategy of early surgery versus conservative management is associated with an improved long-term survival rate, decreased cardiac mortality, and decreased morbidity after diagnosis. This outcome advantage suggests that early surgery is a reasonable treatment option to be considered in low-risk candidates with repairable valves and severe mitral regurgitation.     

Mild traumatic brain injury--the Fife perspective

Excretion was studied of catecholamines and diphenilamine (DOPA) in 310 patients with carcinoma of the stomach and large intestine and 43 patients with non-malignant diseases. The oncological patients showed decrease in activity of the mediator link of the sympathoadrenal system (SAS) as well as its reserves but there was no association with sex, age, location or histological structure. Three types of SAS functioning were identified, such as compensation, overstrain and emaciation. Surgical intervention led to activation of the hormonal link and exhaustion of the system's reserves. Two kinds of sympathoadrenal response to stress were described--adequate and inadequate. In the former type, phases of stress remain as they are, unchanged, as are time periods of formation thereof, while under the latter one time periods of the phases formation or formation thereof get disordered.     

Antisense estrogen receptor RNA expression increases epidermal growth factor receptor gene expression in breast cancer cells

In human breast cancer, progression to a more malignant phenotype is often accompanied by decreased expression of estrogen receptor (ER) and increased expression of epidermal growth factor receptor (EGFR). Higher levels of this receptor tyrosine kinase are found in tumors lacking ER, and a quantitative, inverse relationship exists between the level of ER and EGFR mRNA in human breast cell lines. Antisense ER (ASER) RNA was used to evaluate the consequence of decreased ER expression in breast cancer cells, specifically to determine whether ER is involved in the regulation of EGFR gene expression. ER-positive MCF-7 human breast cancer cells were transfected with ASER, and clones constitutively expressing ASER RNA had decreased ER and up to a 3-fold increase in the expression of EGFR mRNA. To confirm that this observation was a direct consequence of ASER expression, a metal-inducible ASER expression construct was transfected into MCF-7 cells, and transfected clones were isolated and characterized. Northern analysis revealed an induction of ASER RNA within 1 h of the addition of zinc, which was followed by a 4-fold increase in EGFR mRNA levels, maximal at 6-12 h. The basal level of expression of the glucocorticoid receptor is also inversely related to that of ER among breast cancer cell lines, but neither constitutive nor inducible expression of ASER affected the expression of glucocorticoid receptor. These data support the hypothesis that the level of expression of ER specifically influences the expression of EGFR in human breast cancer cells and provides a potential link between loss of steroid sensitivity and the acquisition of autonomous growth.     

An evaluation of the allergic contact dermatitis potential of colloidal grain suspensions

OBJECTIVE: To assess the efficacy of Kangke Injection in treating viral myocarditis. METHODS: Kangke Injection is the effective ingredient extracted from Radix Sophora flavescens (RSF). Seventy-six cases of virus myocarditis suffering from the continuous positive Coxsackie B virus ribose nucleic acid-polymerase chain reaction (CBVRNA-PCR) in blood, their peak value in blood was determined by high performance liquid chromatography (HPLC) and compared with 50 cases treated by glucose-insulin-potassium chloride (GIK). RESULTS: The clearance rate of CBVRNA-PCR and RSF was dose-dependent. The effective rate of RSF on palpitation, chest distress, dispnea was 96.02%, and that of arrhythmia was 100%, all of them were better than those of control. After RSF therapy, the parameters of heart function of ejection fraction (EF), stroke volume (SV), cardiac output (CO), and cardiac index (CI) elevated significantly (P < 0.01), left ventricular mass (LVM) and left ventricular mass index (LVMI) were decreased statistically significantly, while after 5 month therapy, the anti-Coxsackie group B virus neutralizing antibodies of RSF group was returned to normal titer, natural killer (NK) cell activity elevated, P < 0.01. CONCLUSION: RSF was an effective substance for regressing the "Pathologic status" of viral myocarditis.     

Central poststroke pain and Wallenberg''s lateral medullary infarction: frequency, character, and determinants in 63 patients

BACKGROUND: Questionnaire-based surveys from several countries have consistently detected adverse health associated with home dampness and mould growth. METHODS: To test the validity of questions commonly used to indicate the presence of indoor mould, questionnaires were administered in 403 homes where dust samples were taken for viable fungi and air samples for ergosterol. RESULTS: Geometric mean concentrations of the total viable fungi were 255 (SE 116) x 10(3) CFU/g when mouldy odours were reported and 155 (SE 55) when odours were not reported (P = 0.01). Similarly, reported water damage was associated with a 50% increase (P = 0.06). Geometric mean concentrations of the predominantly indoor-source fungi, Aspergillus plus Penicillium, were twice as high when mould or mildew was reported than when not mentioned (P = 0.01). The presence of reported mould or water damage was unrelated to the presence of detectable levels of ergosterol. There was evidence for reporting bias: in the presence of low concentrations of viable fungi in dust, respondents reporting allergies were more likely to report visible mould growth (odds ratio [OR] = 1.8, 95% confidence interval [CI]: 0.9-3.5, P = 0.10. In the presence of elevated concentrations of dust fungi, respondents who smoked were less likely to report visible mould growth, (OR = 0.4, 95% CI: 0.2-0.7, P = 0.005). CONCLUSIONS: Reported mould, water damage, and mouldy odours were associated with elevated levels of indoor fungi. However, inaccuracy was high and there was evidence of a systematic reporting bias. Future research should concentrate on developing accurate objective measures of exposure to fungi, and then use this information to develop valid questionnaires. Currently, objective measures not questionnaires, are recommended to clarify the health effects of indoor fungi.     

Coronary artery disease in women. How customary expectations can interfere with interpretation of test results

Although one in three women in the United States will die of heart disease, traditionally coronary artery disease (CAD) in women has received less recognition as a public health problem than has the disease in men. To assist practicing physicians in recognizing CAD in women, this article reviews sex differences in risk factors and manifestations of CAD as well as strengths and weaknesses of various diagnostic tests in women.