Medical education in substance-related disorders: components and outcome

Aims. To analyze the process of acquisition by physicians of a body of knowledge and skills in the management of substance abuse. Design. A comprehensive search of English-speaking literature was conducted over 20 years. Articles assessing the outcome of educational strategies in undergraduate, graduate and continuing medical education were examined to determine the targeted sample, the educational strategies involved and the outcomes assessed. Findings. Nine studies in undergraduate education, 11 in graduate and 11 in continuing education met the inclusion criteria. They were generally difficult to compare in design, strategy and outcome analysis. Cognitive knowledge and behavioral skills appear to be easier to obtain compared to more complex attitudinal shifts. Conclusions. There is growing consensus in the selection of a combined didactic and interactive educational strategy but few empirical data as to the more cost-effective learning interventions. Training must be reinforced at regular intervals. While the expanding panoply of interventions available to physicians should enhance the perceptions of role legitimacy and treatment optimism, cohort studies across levels of education, specialty groups and across-substance and other addictive behaviors are required to determine cost-effective educational strategies.     

Decellularized dermis in combination with cultivated keratinocytes in a short- and long-term animal experimental investigation

Decellularized human dermis as a potentially ideal scaffold for dermal substitution in severe burns was examined in a two‐staged animal experiment. In an initial step, an in vitro generated composite graft consisting of human keratinocytes and decellularized dermis (AlloDerm®) was transplanted onto nude mice in a short‐term trial (n = 20, 14 days). Subsequently, a combined one‐step grafting of full thickness wounds with both decellularized dermis (in part preincubated with fibroblasts) and cultivated autologous keratinocytes as a cell suspension in fibrin glue was done in a long‐term porcine animal model (n = 10, 6 months). In both series, macroscopic wound healing was evaluated by planimetry. Histological investigations included morphological as well as immunohistochemical parameters. The short‐term study showed both successful integration of the composite grafts and reduction of wound contraction compared with the control group (epithelial grafts). The long‐term porcine study displayed reduced myofibroblast formation and contraction in the wounds that had been treated with fibroblast‐preincubated dermis. After 4 weeks, a decline of the structural integrity of the dermal matrix could be noticed. The utility of decellularized dermis as template for both dermal reconstitution and keratinocyte delivery vehicle was shown. The closure of full thickness wounds by a single‐step combination of an autologous keratinocyte fibrin sealant suspension and acellular dermis in a pig animal model could be shown. Incorporation of fibroblasts led to reduced wound contraction but could not prevent the loss of dermal integrity. The engineered ‘skin’ remained viable and stable over a period of 6 months.     

Interferon-gamma activates rat alveolar macrophages for anticryptococcal activity

Cryptococcus neoformans is a pathogenic yeast causing disease predominantly in immunosuppressed patients. C. neoformans is acquired by the pulmonary route, where the alveolar macrophage (AM) is a resident mechanism of host defense. The ability of rat AM to be activated by products of the immune response for enhanced anticryptococcal effect has not previously been demonstrated. Rat AM could be activated in vitro for anticryptococcal activity by medium conditioned by concanavalin A-stimulated splenic lymphocytes. A monoclonal antibody that neutralizes interferon-gamma (IFN-gamma) inhibited the macrophage-activating activity of lymphokine-containing medium (LCM). Further, recombinant IFN-gamma activated AM for anticryptococcal activity. The concentration of IFN-gamma in LCM, determined by enzyme-linked immunosorbent assay, was equivalent to the range of concentrations of recombinant IFN-gamma which activated AM. Thus, IFN-gamma was necessary and sufficient for optimal macrophage activation by medium conditioned by proliferating lymphocytes. Lipopolysaccharide could not enhance the anticryptococcal activity produced by optimal concentrations of LCM or IFN-gamma but did augment the effects of submaximal stimulation. Both LCM and recombinant IFN-gamma increased the percentage of macrophages with cell-associated cryptococcus, suggesting that activation of AM enhanced the adhesion or uptake of cryptococcus. We speculate that inadequate availability of lymphokines such as IFN-gamma may result in the immunodeficient state in hosts unable to generate an appropriate response to cryptococcal antigens. Administration of lymphokines such as IFN-gamma to immunosuppressed hosts might circumvent the defect in cell-mediated immunity.     

Dural fistulas involving the cavernous sinus: results of treatment in 30 patients

Thirty symptomatic indirect carotid cavernous fistulas were treated between 1978 and 1986 with a variety of treatment modalities. Combined carotid artery and jugular vein compression resulted in a complete cure in seven of 23 patients (30%) and improvement in one additional patient. There were no complications from this treatment, which is performed by the patient on an outpatient basis. Patients in whom carotid jugular compression therapy failed or who demonstrated cortical venous drainage or visual decline were treated with intravascular embolization. Embolization resulted in complete cure in 17 of 22 (77%) and improvement in four of 22 (18%). One patient required surgical excision of the involved dura after embolization to achieve complete cure. There was one permanent complication (stroke), which resulted in mild weakness caused by clot formation on a catheter.     

Bezold-Jarisch reflex in postoperative pediatric cardiac surgical patients

The Bezold-Jarisch reflex is an inhibitory reflex that originates from the heart, is mediated by the vagus nerve, and is manifested by hypotension and bradycardia. We present 4 pediatric cardiac surgical patients, aged 1 day to 9 months, who exhibited cardiovascular collapse in their early postoperative course. In each patient, cardiovascular deterioration was marked by an insidious decrease in arterial blood pressure without an associated change in heart rate, central venous pressure, or airway pressure. Bradycardia followed the decrease in blood pressure. The Bezold-Jarisch reflex was suspected and atropine was administered, first as a bolus injection at 0.01 mg/kg, and later, as a continuous infusion at 0.01 mg.kg-1.h-1. Atropine prevented recurrent episodes of hypotension and bradycardia. We believe the Bezold-Jarisch reflex is more prevalent than previously suspected in postoperative pediatric cardiac surgical patients.     

Blood group A immunodeterminants on human red cells differ in biologic activity and sensitivity to alpha-N-acetylgalactosaminidase

BACKGROUND: Epitopes of blood group A antigen can be enzymatically cleaved from red cells (RBCs), but the extent of cleavage required for normal survival in allogeneic blood transfusion recipients is unknown. Therefore, the cleavage rates were studied for A antigen epitope binding of 1) complement-activating anti-A, 2) Dolichos biflorus anti- A, lectin, and 3) hemagglutinating anti-A during incubation with a purified alpha-N-acetylgalactosaminidase, E.C. 3.2.1.49 (alpha- GalNAc'ase). STUDY DESIGN AND METHODS: Suspensions of group A RBCs were incubated with alpha-GalNAc'ase. Cells were removed at intervals, washed, and tested for loss of binding by monoclonal, polyclonal, and complement-activating anti-A, D. biflorus anti-A1 lectin, and Ulex europaeus anti-H lectin. RESULTS: A epitopes binding D. biflorus lectin were highly susceptible to alpha-GalNAc'ase; simultaneously with their loss, binding with U. europaeus lectin emerged. Loss of complement- mediated hemolysis was slower. A epitopes binding hemagglutinating anti- A were most resistant. Cleavage of A epitopes from membrane glycosphingolipids with short oligosaccharide chains was similarly resistant. Rates of cleavage from A1 and A2 RBCs were similar. CONCLUSION: RBC epitopes of blood group A differ in susceptibility to cleavage and biologic reactivity, which suggests that subsets mediating important biologic functions exist on functionally and topographically distinct membrane glycoconjugates.     

Potential increased risk of virus transmission due to exclusion of older donors because of concern over Creutzfeldt-Jakob disease. The National Heart, Lung, and Blood Institute Retrovirus Epidemiology Donor Study

BACKGROUND: Concern over the theoretical possibility of disease transmission via blood from donors who develop Creutzfeldt-Jakob disease has led to proposals to exclude older individuals from donating plasma for further manufacture into pooled plasma donations. The impact of extending this age-deferral policy to blood donors was examined with respect to the risk for known transmissible viruses. STUDY DESIGN AND METHODS: Demographic characteristics and confirmed prevalence rates (/10(5) first-time donations) and incidence rates (/10(5) person-years for repeat donors) for viral markers were compared for donors < 50 years old (n = 1,259,805 [85%]) and > or = 50 years old (n = 219,856 [15%]) and for donors < 60 years old (n = 1,409,176 [95%]) and > or = 60 years old (n = 70,485 [5%]). Incidence rates were combined with infectious window-period estimates for each virus, to calculate the risk of virus transmission per 10(6) donations. RESULTS: Unadjusted prevalence rates were significantly greater for younger than for older donor groups for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) (p < or = 0.05). Incidence rates (and transmission risk estimates) for HBsAg were significantly higher in the < 50 donor group than in the > or = 50 group (p < or = 0.05), and those for HIV, human T-lymphotropic virus, and HCV were not significantly higher (p > 0.05). Blanket removal of donors over the age of 50 would potentially lead to the following significant increases in the risk of infected units: HIV, 12 percent; HCV, 21 percent; and hepatitis B virus (HBsAg), 22 percent. CONCLUSION: Removal of donors over the age of 60 would not significantly affect the risk of infected units. Deferral of donors > or = 50 years of age from whole-blood donations for unfounded concerns about Creutzfeldt-Jakob disease could have adverse effects on both blood availability and safety.