Cardiovascular Medicine at the University of Minnesota: Lost and then Found in Translation

Translational research requires basic innovation and development, an infrastructure for deployment to the experimental clinical arena and a distribution system to connect patients to innovation. The University of Minnesota cardiovascular program led the way in translational medicine after World War II. Subsequently, it briefly lost its way. Learning from the lessons of the past, cardiovascular medicine at Minnesota is being reborn as a twenty-first century organization developing medical innovation from ideas and translating the product to patients in a complex healthcare system.     

Plasma testosterone stimulation-suppression dynamics in hirsute women. correlation with long-term therapy

Clinical response and changes in plasma testosterone were measured in 22 hirsute women during the administration of dexamethasone, ethinyl estradiol-medroxyprogesterone, or both. The response of plasma testosterone to the administration of adrenocorticotropic hormone (ACTH), human chorionic gonadotropin (HCG) and dexamethasone was measured before treatment in 16 patients, and six additional patients were treated without initial testing. Patients were treated with three month courses of each therapy, regardless of their test results. Results of short-term testing did not correlate with those of long-term treatment. Previously elevated testosterone levels were suppressed in 80 per cent of the patients treated with dexamethasone and in all the patients treated with ethinyl estradiol-medroxyprogesterone (EE-MP).Hirsutism diminished in a third of the patients treated with dexamethasone and in half of the patients treated with EE-MP. Acne diminished in half of the patients with either therapy. There was good correlation between normalization of plasma testosterone levels and clinical improvement.Normal plasma testosterone levels were maintained for several months after dexamethasone treatment was discontinued.Recommendations are given for the approach to diagnosis and treatment of the female patient with hirsutism.     

Normalization of urinary oxalate by taurine in glycolate-fed rats

Oral feeding of sodium glycolate (50 mg/d/rat for ten days) caused a significant (P less than 0.001) increase in oxalate and taurine excretion and a decrease in liver protein content (P less than 0.05), glycolic acid oxidase levels (P less than 0.01), and glycolic acid dehydrogenase levels (P less than 0.01) as compared to normal untreated rats. Taurine (100 mg/d/rat), when administered along with glycolate, prevented these effects of glycolate as evident from normal urinary excretion of oxalate, liver protein content, glycolic acid oxidase, and glycolic acid dehydrogenase levels in glycolate- plus taurine-fed animals.     

Hemiagenesis of the thyroid gland.

Three patients with hemiagenesis of the typhoid gland are described. One was clinically euthyroid, whereas the other two were more unusual in that one had coincident Graves' disease with thyrotoxicosis, and one had primary myxodema. In all three cases diagnosis of hemiagenesis was established by the administration of thyroid-stimulating hormone (TSH). The literature on hemiagenetic thyroid glands with and without associated thyroid disease is reviewed. Although the anomaly is uncommon, awareness and recogniton of its existence may clarify an otherwise puzzling clinical thyroid evaluation, and thus possible avert an unnecessary surgical procedure.     

Left ventricular dysfunction after acute myocardial infarction: results of a prospective multicenter study

In a multicenter prospective study of 866 patients who survived the coronary care unit phase of an acute myocardial infarction, variables reflecting left ventricular function were examined to assess their impact on 2 year survival. Single variables that reflected left ventricular dysfunction before infarction and in the acute and recovery phases were, respectively, history of prior myocardial infarction, rales in the coronary care unit dichotomized at greater than bibasilar and predischarge radionuclide ejection fraction dichotomized at less than 0.40. When combined in a stepwise fashion, patients lacking these three risk characteristics had a 2 year 4.2% mortality rate, whereas patients possessing all three characteristics had a 45% mortality rate. Rales in the coronary care unit and predischarge ejection fraction act independently, and each contributes to mortality. Fifty-two patients with advanced rales but an ejection fraction of 0.40 or greater had a 21% mortality rate. Similarly, 208 patients with few rales but an ejection fraction of less than 0.40 had a 15% mortality rate. These data suggest that the mortality risk imposed by those factors that assess permanent left ventricular damage is independent of and additive to the mortality risk contributed by dynamic, acute phase dysfunction. These data fit the hypothesis that acute phase dysfunction is, in part, due to transient ischemia that, on reversal, can restore function toward normal. The results suggest 1) that assessment of left ventricular function during the acute and recovery phases of myocardial infarction is necessary to define prognostic characteristics of an individual patient, and 2) that of particular importance is the identification of patients whose postinfarction course is consistent with reversible ischemia.     

Evaluation of the effects of catheter sampling for the study of platelet behavior in the pulmonary and coronary circulation

To study the effects of sampling through cardiac catheters on indices of platelet function, we measured the levels of platelet factor 4 (PF₄), beta thromboglobulin (BTG), and platelet aggregate ratio (PAR) in 10 patients with atrioventricular accessory pathway (AVNAP), six patients with primary pulmonary hypertension (PPH), and six patients with critical narrowing of the left anterior descending artery (LAD). In AVNAP and LAD patients samples were drawn simultaneously from a peripheral vein, coronary sinus, and brachial artery; in AVNAP patients samples were also obtained from the axillary vein before the coronary sinus was entered. In PPH patients samples were drawn from pulmonary artery, aorta, and a peripheral vein; in these patients the effects of an intravenous infusion of prostacyclin (PGl₂) (2 to 8 ng/kg/min) on PF₄, BTG, and PAR were also studied at all sampling sites. In all patients arterial, coronary sinus, pulmonary arterial, and axillary venous levels of PF₄, BTG, and PAR significantly exceeded those measured in the peripheral vein. PGl₂ infusion resulted in a significant decrease of PF₄ at all sampling sites, while no consistent BTG changes were observed and PAR levels did not decrease in the peripheral vein. Although a considerable interpatient variability in PF₄ levels was observed, a significant (r = 0.91) correlation was found in patients with AVNAP between simultaneous coronary sinus and arterial PF₄ levels. The value of PF₄ coronary sinus-arterial difference in LAD patients was consistently higher than that calculated in AVNAP patients (54.5 ± 28.9 vs 4.2 ± 3.8 ng/ml). In conclusion: (1) a considerable and variable degree of platelet activation occurs with catheter sampling, preventing the measurement of absolute levels of platelet metabolites; (2) among the indices examined PF₄ appears the most sensitive for detecting changes in platelet activity; and (3) the measurement of coronary sinus-arterial PF₄ differences may provide information on directional changes in transcardiac platelet behavior.     

Turnover of apoproteins A-I and A-II of high density lipoprotein and the relationship to other lipoproteins in normal and hyperlipidemic individuals

The kinetics of the major apoproteins of high density lipoproteins (HDL), A-I(apoA-I) and A-II(apoA-II), were studied from the specific activity-time curves of these apoproteins, after reinjection of radioiodine-labeled HDL. In all 20 subjects, HDL apoprotein kinetics conformed to a two-pool model. The total fractional removal rates for the two apoproteins were similar, although the irreversible fractional removal rate appeared to be slightly greater for apoA-I. The mean transport for A-I and A-II was 12.2 mg/kg/day and 5.0 mg/kg/day, respectively. The mass of the apoprotein pools was strongly correlated with apoprotein production rate and also, to a lesser degree and inversely, with the irreversible fractional catabolic rate. Transport was directly correlated with body weight. Higher fractional catabolic rates, including the transfer rates between the two pools, were observed in five hypertriglyceridemic subjects; in contrast, five subjects with familial hypercholesterolemia tended to show lower fractional catabolic rates. These findings were supported by (1) a strongly positive correlation between the transport rates of HDL A-I and of very low density lipoprotein (VLDL) apoB, determined simultaneously in 10 subjects; and (2) a significant inverse correlation between the irreversible fractional removal rate of HDLA-I and the concentration of low density lipoprotein (LDL) apoB, measured in 15 subjects. These observations underline the metabolic interrelationships of the major lipoprotein classes. Two subjects with familial hyperalphalipoproteinemia showed enlarged pool sizes, but normal transport, with irreversible fractional removal rates that were in the lower range for the group of 20 subjects.     

Épistémologie psychanalytique : une épistémologie aux frontières

ObjectivePsychoanalysis and epistemology raise multiple questions, and provoke debate and lively controversies. Without wishing to take up the old debate on the scientific nature of psychoanalysis, we wish to question its place in a contemporary epistemology, an epistemology of research, rather than one of science. We propose to think about psychoanalytic epistemology on the borders: between the theoretical and the clinical, between research and the practice of the cure, but also in dialogue with other hybrid disciplines such as psychiatry.MethodStarting from the observation that progress in scientific disciplines such as physics has led to the abandonment of the illusion of a universal theory of knowledge and to the shattering of the affirmation of epistemology's unique conception, we study the specificities of psychoanalytic epistemology as well as current conceptions of epistemology in science, research, and evaluation. We are interested in metapsychology as a Freudian epistemology, as well as in its limits and the criticisms it raises.ResultsPsychoanalysis carries a specific form of knowledge based on the hypothesis of the unconscious. It is a hybrid object with a hypercomplex causality that mixes nature, culture, and the clinic. Thinking about its epistemology roots us in the processual logic of the notion of epistemological obstacle, as opposed to epistemological impasse. The liveliness of psychoanalytical epistemology rests both on its confrontation with clinical practice, and with the progress of other sciences such as the chaos sciences, which open up to non-linear causalities and take dissipative structures into account. The epistemology of research in psychoanalysis requires compromise but also makes “border work” possible; here, a metapsycho-epistemological gap is put to work.DiscussionThe possibility of a psychoanalytical epistemology is not unanimously accepted. The best-known skeptic is perhaps K. Popper, whose proposals on the criteria of scientificity were ultimately refuted by epistemologists of the physical sciences. Scientific models’ lack of uniqueness makes the exclusive recourse to the experimental model based on the triptych observation-hypothesis-verification obsolete from an epistemological point of view. Its epistemological specificity lies in its method, which articulates the theory of unconscious processes with a transference-based clinical practice, making it a regional epistemology. The epistemology of psychoanalysis is situated at the borders of the natural and the cultural, the individual and the intersubjective, science and fiction, hermeneutics and phenomenology, clinical practice and research. Its multiple borders are, according to the times and the theoretical choices, more or less open or even porous, more or less closed or even impassable.ConclusionPsychoanalysis's epistemological stakes reflect the contemporary evolution from an epistemology of science to an epistemology of research and therefore of evaluation. The hypercomplex nature of the human psyche and of psychic facts makes the transposition of epistemic models from other sciences inadequate. The border position of psychoanalytic epistemology cannot be limited to a form of causalist and theoretical originality; it is first and foremost rooted in the specificity of its method, which is itself on the border between practice and theory. The processual part of psychoanalysis as a theory, but also as a therapy, is essential and thus opens to a questioning of the transmission of psychoanalytic epistemology to the field of research, to the sciences as a whole. The wager of the transmissibility of the epistemology of psychoanalysis remains a challenge but we consider that thinking about it as a dialogue – that is, a confrontation with and an opening-up to other disciplines – is necessary in this between compromise and border work.     

1 + 1 = 3? The systematic development of a theoretical and evidence-based tailored multimedia intervention to improve medication adherence

Objective

To describe the development of a theoretical and evidence-based tailored multimedia intervention to improve medication intake behavior in patients with inflammatory bowel disease (IBD). The intervention integrates interpersonal and technology-mediated strategies with the expectation that this will work synergistically.

Methods

The development followed the Medical Research Council's framework. Three literature reviews and three pre-tests among 84 IBD patients and eight nurses were conducted to guide the development of the intervention. A feasibility study was carried out among four nurses and 29 patients.

Results

The components include: (1) an online preparatory assessment (OPA); (2) tailored interpersonal communication; and (3) tailored text messaging. To support the development, the feasibility was tested. Results indicated that the OPA was comprehensive and could be a helpful tool for both patients and nurses to prepare for the consultation. The training was evaluated as being instructive and applicable with a mean mark of 8.5. Of the developed messages, 65.6% received positive evaluations and were used in the intervention.

Conclusion

By applying the framework, we were able to describe the logic behind the development of a tailored multimedia intervention to improve medication intake behavior.

Practice implications

This study could serve as a guide for the development of other health interventions.