DNA-based vaccines: new possibilities for disease prevention and treatment.

Ottawa researcher Dr. Heather L. Davis has become a pioneer in the development of DNA-based vaccines. With her collaborators in France and Germany Davis found that introducing the DNA code for the envelope protein of the hepatitis B virus into the muscle tissue of mice prompted a strong and sustained immune response. She believes that DNA-based vaccines could prove to offer many advantages over conventional vaccines, not least of which are greater safety and effectiveness and reduced cost. She has also begun to explore the potential of DNA-based vaccines for use in the treatment of disease. In recent experiments Davis and colleagues in France have successfully used DNA vaccination to cure transgenic mice of a chronic hepatitis B carrier state.     

The Solution Method: 2-year trends in Weight, Blood Pressure, Exercise, Depression, and Functioning of Adults trained in Development Skills

This study describes changes observed during a 2-year period in participants enrolled in The Solution Method, a developmental skills training program for adult weight management. This Intervention is the adult application of a model of treatment previously used only in the management of pediatric obesity (The Shapedown Program). Developmental skills training integrates understandings and methods from developmental, family systems, biomedical, genetic, and behavioral theories of the etiology of obesity. Twenty-two subjects (mean age=43.4±8.5 years and mean body mass index=33.1+5.3) completed a group intervention based on this method, which was conducted by a registered dietitian and a mental health professional. Questionnaire responses indicated the extent to which their weight was a medical and/ or psychosocial risk. Subjects attended 2-hour weekly sessions for an average of 18 weeks during which they were trained in six developmental skills: strong nurturing, effective limits, body pride, good health, balanced eating, and mastery living. Data, which were collected at the beginning of treatment and at 3, 6, 12, and 24 months, included weight, blood pressure, 7-day exercise recalls, and responses to depression and functioning (psychosocial, vocational, and economic) questionnaires. Participants’ weights decreased throughout the 2-year period of the study: mean weight change was −4.2 kg (3 months), −6.0 kg (6 months), −7.0 kg (12 months), and −7.9 kg (24 months). In addition, compared with baseline values, systolic and diastolic blood pressure, exercise, and depression improved throughout the study period. These improvements were statistically significant at 24 months for weight (p<.01), systolic blood pressure (p<.02), diastolic blood pressure (p<.001), and exercise (p<.001); the results were not statistically significant for depression. Most participants reported improvement in a broad range of aspects of functioning. We conclude that this application of developmental skills training for adult weight management may produce significant long-term beneficial effects. J Am Diet Assoc. 1997;97:1133–1138.     

Serum and Plasma Markers of Nutritional Status in Children Infected with the Human Immunodeficiency Virus

Objective To determine whether reduced serum or plasma protein and micronutrient levels are common in children infected with the human immunodeficiency virus (HIV) and whether these levels are different in children with growth retardation compared to those with normal growth.

Subjects Children were separated into three groups: (a) HIV-infected with growth retardation (HIV+Gr); (b) HIV-infected with normal growth (HIV+); (c) HIV-uninfected with normal growth (HIV-). All children were afebrile and free of acute infection at the time of study. During a 24-hour stay in the Pediatric Clinical Research Unit, blood was drawn for analysis of total protein, albumin, zinc, selenium, and vitamin A levels; growth measurements were obtained; and dietary intake was assessed by 24-hour weighed food intake and 24-hour dietary recall.

Statistical analysis Mean differences between groups were assessed by analysis of variance, and differences in the frequency of nutrient deficiency were determined by χ² analysis.

Results Thirty-eight children between 2 and 11 years of age were studied: 10 HIV+Gr, 18 HIV+, and 10 HIV-. No statistically significantly differences were noted in mean levels of albumin, prealbumin, zinc, and selenium. Mean serum level of vitamin A was significantly higher in the HIV+Gr group than in the other two groups. There were no significant differences between groups in the frequency of deficiency for any nutrient studied. Mean energy and nutrient intake was similar among groups.

Applications/conclusions Abnormal serum or plasma protein or micronutrient levels were uncommon in this cohort of HIV-infected children, even in children with growth retardation. Routine monitoring of the level of proteins and micronutrients studied is unnecessary in the absence of specific clinical indicators of deficiency. J Am Diet Assoc. 1997-97:1377-1381.     

Computer-Assisted Instruction Improves Clinical Reasoning Skills of Dietetics Students

Objective The effects of a computer-assisted instruction (CAI) tutorial program on learning clinical reasoning skills were compared in undergraduate dietetics students.Design A drill-and-practice program to control for time on task, a tutorial program, and a simulation program, as the test vehicle, were developed. The tutorial and simulation programs presented data on a patient with cardiovascular disease.Setting Subjects were tested in 30 undergraduate dietetics programs.Subjects Participants were 413 undergraduate diet therapy students enrolled in a coordinated program in dietetics (CPD) or a didactic program in dietetics (DPD).Intervention After completion of lectures on cardiovascular disease, subjects were given the drill-and-practice program plus a simulation test (group 1), the tutorial plus a simulation test (group 2), or the simulation test only (group 3).Main outcome measures Scores on the simulation test were compared. Variables included type of CAI, dietetics program, year in school, computer experience, and experience using a medical chart. Mastery of objectives related to lower- and higher-level clinical reasoning skills introduced in the tutorial program was compared.Statistical analysis One-way analysis of variance and Student-Newman Keuls tests were conducted to determine any differences among the three groups. Reliability was determined using the Kuder-Richardson Formula 20.Results The reliability coefficient of the simulation test was 0.93. Group 2 scored higher on the simulation test than group 1 or group 3. As a group, the CPD students scored higher than the DPD students. When CPD and DPD students were divided into the three experimental groups, there was no significant difference between the CPD and DPD student simulation scores. Group 2 mastered all objectives for lower-level reasoning skills and the higher-level decision-making objective better than groups 1 and 3.Applications/conclusions A computer tutorial program enhanced clinical reasoning skills in undergraduate dietetics students. This type of program could be used to supplement many topics taught in diet therapy and provide DPD students with experiential learning before their clinical intern practicums. J Am Diet Assoc. 1995; 95:868–873.     

Nutrition Management of Patients with Epidermolysis Bullosa

Epiderrnolysis bullosa (EB), a heterogeneous group of rare, inherited disorders, is manifested by recurrent blistering of the skin induced by the slightest trauma. Little information exists regarding the nutrition management of patients with EB. This study presents information on growth, identifies potential nutrition problems, and provides guidelines for nutrition management of persons with EB. Eighty patients attending a dermatology clinic for EB patients are described. Severity of disease ranged from mild blistering of the knees, elbows, and feet to extensive blistering and scarring of the skin and entire gastrointestinal tract. Of the 18 children with EB simplex, which is a mild form of the disease, 4 (22%) were at nutritional risk. None of the 13 adults with EB simplex were underweight and 8 (62%) were overweight. Of the patients with the more severe forms of EB, 27 of the 35 (77%) children with dystrophic EB and 4 of the 7 (57%) children with junctional EB were at risk for malnutrition. Of the 7 adults with dystrophic EB, 6 (86%) were underweight. Common nutrition problems included protein-energy malnutrition, chewing and swallowing problems, constipation, anemia, and vitamin/mineral deficiencies. When nutrition care protocols address these problems, growth, development, and nutritional status can improve. For those with severe nutrition problems, gastrostomy feeding or similar nutrition therapies should be considered. J Am Diet Assoc. 1995; 95:575-579.     

Validation in the sheep of an ultrasound velocity dilution technique for haemodialysis graft flow

BACKGROUND: A simple, rapid, inexpensive method for measuring the flow in a patient's vascular access would permit routine monitoring during haemodialysis, and hence provide information of access graft deterioration sufficiently early to increase the success of minimally invasive remedial procedures. This paper reports the validation of such a method in animals. METHODS: A PTFE graft was implanted in sheep between the carotid artery and the jugular vein. While the sheep was under general anaesthesia and on an haemodialysis circuit, ultrasound velocity in its blood was perturbed by the injection of a 5-10 ml bolus of isotonic NaCl. The pump tubing flow was measured by a transit-time blood flow meter. This flow was combined with the areas of perturbation generated by the injection before and after mixing in the access flow to estimate graft flow. The calculated graft flow was compared to flow measured directly by a transit-time probe on the same carotid artery. RESULTS: Over a 10-fold range, 120-1260 ml/min, graft flow measured by ultrasound velocity dilution agreed well with graft flow measured directly with a scatter of 76 ml/min about the regression line. CONCLUSION: Ultrasound velocity dilution provides a method for measuring flow in the graft accurate enough for clinical evaluation of patients on dialysis.      

Selective inhibition of T cell proliferation but not expression of effector function by human alveolar macrophages

BACKGROUND: Alveolar macrophages are thought to play an important part in regulating lung immune responses. While it is clear that human alveolar macrophages suppress T cell proliferation in vitro, the mechanisms by which this is achieved are not clear, nor is it known whether alveolar macrophages also inhibit other aspects of T cell function. METHODS: Peripheral blood mononuclear cells were stimulated with phytohaemagglutinin or house dust mite allergen, and cultured with variable numbers of autologous alveolar macrophages obtained by bronchoalveolar lavage from 20 normal subjects. RESULTS: Alveolar macrophages induced a reversible inhibition of T cell proliferation in response to both mitogen and allergen stimulation, with the latter being considerably more susceptible to inhibition. This was achieved via heterogenous mechanisms, involving both soluble factors derived from alveolar macrophages and cell-cell contact. Despite inhibiting proliferation, alveolar macrophages had little or no effect on T cell calcium flux, the characteristic changes in CD3, CD2, CD28 and interleukin-2 (IL-2) receptor expression which accompany normal T cell activation, and IL-2 and interferon gamma secretion. In contrast, alveolar macrophages inhibited the tyrosine phosphorylation of proteins which may be involved in IL-2 receptor-associated signal transduction. CONCLUSIONS: The immunoregulatory properties of alveolar macrophages are relatively selective, allowing T cell activation and cytokine secretion while inhibiting T cell proliferation within the lung.