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Biomedical subjects

D Leonard

Publications and source records attributed to D Leonard.

70 records · Page 4Linked to original sources
PubMed1986

Identification of the direct vasodilator effect of milrinone with an isolated limb preparation in patients with chronic congestive heart failure.

We developed an isolated limb preparation to evaluate the direct vasoactive properties of cardioactive drugs on the forearm vasculature in patients with congestive heart failure. Using this model, we infused milrinone in subsystemic doses (1, 10, and 20 micrograms/min per 100 ml forearm volume [FAV] ) into the brachial artery of 13 patients with moderate-to-severe congestive heart failure. We monitored forearm hemodynamics, systemic hemodynamics, and milrinone plasma concentration from both the forearm venous effluent and pulmonary artery. This preparation enabled us to assess the direct forearm vascular response to milrinone. Compared with baseline forearm blood flow (2.46 +/- 1.37 ml/min/100 ml FAV), the three doses of milrinone resulted in increases in forearm blood flow to 2.66 +/- 1.43, 4.21 +/- 1.79, and 6.73 +/- 3.69 ml/min/100 ml FAV. This was associated with a reduction of forearm vascular resistance from the baseline value of 52 +/- 38 U to 47 +/- 36, 25 +/- 13, and 17 +/- 10 U. The p value for the difference in response of flow and resistance after the 10 and 20 micrograms doses vs that at baseline was .05. This forearm vasodilatation occurred without change in systemic hemodynamics or therapeutic milrinone plasma concentrations in the pulmonary artery. In five patients, we compared the response to intra-arterial milrinone with that of nitroprusside. At a dose of 10 micrograms/min/100 ml FAV, the response to nitroprusside (7.20 +/- 3.24 ml/min/100 ml FAV) was greater than that to milrinone (4.65 +/- 2.18 ml/min/100 ml FAV) (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Acute dose range study of milrinone in congestive heart failure.

To determine the magnitude and time course of the optimal acute hemodynamic response to oral milrinone, an ascending dose range study was performed in 34 patients with severe chronic congestive heart failure (2.5 to 10 mg, n = 21; 7.5 to 15 mg, n = 13). With the 7.5- and 10-mg doses in both groups, cardiac index increased 26%, pulmonary capillary wedge pressure decreased 25% and systemic vascular resistance decreased 20%, with peak effect at 90 minutes. The hemodynamic improvement with 10 mg was sufficient to normalize cardiac index in 29% of patients. There was a clear dose-response relation, with the largest increases of cardiac index seen with the 15-mg dose (1.67 +/- 0.10 to 2.31 +/- 0.11; p less than 0.005). This dose-response relation was confirmed by the correlation of drug levels and change in cardiac index. However, some patients had significant hypotension and tachycardia with the 15-mg dose. Thus, although 10 mg appears to be optimal for most patients, the dose of milrinone should be individualized for all patients.

Administration, Oral↗
PubMed1985

Milrinone in congestive heart failure: acute and chronic hemodynamic and clinical evaluation.

Acute and chronic hemodynamic and clinical responses to milrinone, a new oral inotrope-vasodilator agent, were evaluated prospectively in 37 patients with severe congestive heart failure. The majority of patients (n = 31) had not responded to prior vasodilator therapy, with a substantial number (n = 8) requiring intravenous inotropic support at the time of initial study. All patients showed acute hemodynamic improvement with oral milrinone, and an optimal maintenance dose was chosen for each patient during dose-ranging studies (average dose 48 mg/day). Milrinone was discontinued before follow-up hemodynamic study in 12 patients (because of worsening congestive heart failure in 6 patients, sudden death in 3 patients, arrhythmia in 1 patient and refusal by 2 patients). Hemodynamic effects of milrinone both acutely and after chronic therapy (average 37 days) were compared in the remaining 25 patients. Acutely, mean cardiac index increased from 1.9 +/- 0.5 to 2.5 +/- 0.5 liters/min per m2 (p less than 0.001), and mean pulmonary capillary wedge pressure decreased from 28 +/- 9 to 18 +/- 8 mm Hg (p less than 0.001). When oral milrinone was readministered after chronic therapy, mean cardiac index increased from 1.9 +/- 0.5 to 2.5 +/- 1.7 liters/min per m2 (p less than 0.001), and pulmonary capillary wedge pressure decreased from 27 +/- 8 to 20 +/- 8 mm Hg (p less than 0.001) at 1 hour. New York Heart Association functional class improved in 18 of the 25 patients treated over a long-term period (mean 5.5 +/- 2.3 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1983

The psychological sequelae to disasters.

This article describes the psychological sequelae to disasters with reference to the 1983 'Ash Wednesday bushfires' in the Dandenong mountains of Victoria. Psychological reactions during and after the disaster were varied. The intervention of a mental health team is described.

Anxiety↗
PubMed1978

Blockade of tissue uptake of the antineoplastic agent, doxorubicin.

Myocardial uptake of doxorubicin (Adriamycin) and its inhibition by digoxin and propranolol were studied in paced, isolated perfused cat hearts using tritiated doxorubicin. Contractility was studied using a Walton-Brody strain gauge arch and its first derivative. Coronary blood flow was measured by collecting the effluent from the heart. The myocardial content of doxorubicin was 0.069 +/- 0.101 nmol/mg after 30 minutes. Combined administration of doxorubicin and digoxin reduced the myocardial content of doxorubicin to 0.025 +/- 0.010 nmol/mg (P less than .02). The combination increased contractility compared with doxorubicin alone and increased coronary blood flow compared with digoxin alone. The reduction in the myocardial content of digoxin by doxorubicin was not significant. Propranolol also reduced the myocardial uptake of doxorubicin (P less than .05) without changing coronary blood flow and without further reducing contractility. Thus, both propranolol and digoxin merit evaluation in preventing doxorubicin cardiotoxicity.

Animals↗
PubMed1977

The effect of Candida albicans on the isolation of N. gonorrhoeae.

Recently, several studies have reported that strains of Candida albicans and perhaps other noraml bacterial flora are capable of inhibiting the growth of Neisseria gonorrhoeae in vitro, and it is possible that this may occur in vivo as well. This possible antagonism between N. gonorrhoeae and normal flora microorganisms poses many questions regarding the reliable laboratory diagnosis of gonorrhea. Mixed cultures of C. albicans and N. gonorrhoeae were grown together on GC base agar plates with varying concentrations of nystatin. Recovery of N. gonorrhoeae was improved as nystatin concentration was increased to 25 IU/ml, while growth of C. albicans was effectively inhibited. At concentrations of 50 and 100 IU/ml nystatin also began to inhibit N. gonorrhoeae. There was a noticeable decrease of nystatin bioactivity against C. albicans when the GC plates were stored at 4 C, thus making it more difficult to isolate N. gonorrhoeae. Growth curves of C. albicans and N. gonorrhoeae grown together in liquid medium did not significantly differ from growth curves of the individual organisms. Statistical analysis of our findings does not support the theory that strains of C. albicans produce a soluble diffusible factor that is inhibitory to N. gonorrhoeae.

Amphotericin B↗
PubMedDate not supplied

Gram negative sinusitis: a bacteriologic and histologic study in rabbits.

Recent investigations of chronic sinusitis that is "recalcitrant" to traditional medical and surgical therapy indicate that gram negative bacteria are frequently involved, most commonly Pseudomonas aeruginosa. Analysis of infection-induced histopathologic changes in the underlying sinus mucosa may provide important insight into the recalcitrant nature of these infections. Therefore, the aim of this investigation is to experimentally induce sinus infection in the rabbit with Pseudomonas aeruginosa, a bacterium commonly associated with "recalcitrant sinusitis," and evaluate the histopathologic findings. A unilateral maxillary sinusitis was induced in 33 New Zealand white rabbits. Histologic analysis at 4, 14, 21, and 28 days revealed a moderate inflammation that persisted throughout the study period. Initial changes included edema, loss of submucosal glands, and ulceration. Fibroplasia and bone remodeling were evident throughout the study. Epithelial plaque formation occurred early in the infection, whereas goblet cell formation was a later change. Experimental sinusitis induced by Pseudomonas aeruginosa causes an intense transmucosal injury. The histopathologic injury and response to Pseudomonas aeruginosa appears to be more intense than that noted on previous investigations of experimental sinusitis using other bacteria. The significant histopathologic changes noted could explain the recalcitrant nature of gram negative sinusitis observed clinically in patients.

Animals↗
PubMedDate not supplied

Putting your company's whole brain to work.

Innovate or fall behind: the competitive imperative for virtually all businesses today is that simple. Responding to that command is difficult, however, because innovation takes place when different ideas, perceptions, and ways of processing and judging information collide. And it often requires collaboration among players who see the world differently. As a result, the conflict that should take place constructively among ideas all too often ends up taking place unproductively among people. Disputes become personal, and the creative process breaks down. The manager successful at fostering innovation figures out how to get different approaches to grate against one another in a productive process the authors call creative abrasion. The authors have worked with a number of organizations over the years and have observed many managers who know how to make creative abrasion work for them. Those managers understand that different people have different thinking styles: analytical or intuitive, conceptual or experiential, social or independent, logical or values driven. They deliberately design a full spectrum of approaches and perspectives into their organizations and understand that cognitively diverse people must respect other thinking styles. They set ground rules for working together to discipline the creative process. Above all, managers who want to encourage innovation need to examine what they do to promote or inhibit creative abrasion.

Conflict, Psychological↗
PubMedDate not supplied

Spark innovation through empathic design.

Companies are used to bringing in customers to participate in focus groups, usability laboratories, and market research surveys in order to help in the development of new products and services. And for improving products that customers know well, those tools are highly sophisticated. For example, knowledgeable customers are adept at identifying the specific scent of leather they expect in a luxury vehicle or at helping to tune the sound of a motorcycle engine to just the timbre that evokes feelings of power. But to go beyond improvements to the familiar, companies need to identify and meet needs that customers may not yet recognize. To accomplish that task, a set of techniques called empathic design can help. Rather than bring the customers to the company, empathic design calls for company representatives to watch customers using products and services in the context of their own environments. By doing so, managers can often identify unexpected uses for their products, just as the product manager of a cooking oil did when he observed a neighbor spraying the oil on the blades of a lawn mower to reduce grass buildup. They can also uncover problems that customers don't mention in surveys, as the president of Nissan Design did when he watched a couple struggling to remove the backseat of a competitor's minivan in order to transport a couch. The five-step process Dorothy Leonard and Jeffrey Rayport describe in detail is a relatively low-cost, low-risk way to identify customer needs, and it has the potential to redirect a company's existing technological capabilities toward entirely new businesses.

Commerce↗
PubMedDate not supplied

Gurus in the garage.

Before the days of the Internet, it was primarily venture capitalists who coached young entrepreneurs in Silicon Valley. Today, because of the phenomenal number of new companies, venture capitalists are just too busy. The largest firms still take on a few carefully selected, highly promising zero-stage start-ups, but they simply can't spend the time on ones that aren't going to grow huge quickly. To fill the void, a new breed of adviser has stepped in to coach entrepreneurs. Called mentor capitalists, they help entrepreneurs with everything from recruiting top talent to attracting their first million in seed money. The mentor capitalists in Silicon Valley are cashed-out, highly successful business architects who no longer want to start businesses but who love the thrill of the entrepreneurial game. They spend hours and hours with first-time entrepreneurs, guiding them as they create and refine a business model, test their ideas in the marketplace, build business processes, raise money, and find talent. The authors of this article found through dozens of extensive interviews with entrepreneurs and their coaches that mentor capitalists play many roles: sculptor, psychologist, diplomat, kingmaker, talent magnet, process engineer, and rainmaker. In exchange for small equity stakes, the mentor capitalists wear these different hats, doling out expertise just in time, as situations arise, and in doses appropriate to the situation. Mentor capitalists seed Silicon Valley with expertise and knowledge, augmenting or even substituting for classes in entrepreneurship at local universities. But, as the authors note, the role of the mentor capitalist is essential to any start-up, anywhere.

California↗