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Biomedical subjects

Robert Frank

Publications and source records attributed to Robert Frank.

At least 19 recordsLinked to original sources

Cooperation through moral commitment.

Actions that promote fairness are sometimes consistent with the pursuit of individual self-interest, sometimes not. The diner who leaves a generous tip at a favourite local restaurant, for example, may do so partly out of a sense of obligation to the waiter. But we need not invoke fairness to explain the tip, which is, after all, a prudent investment in obtaining good service in the future. In contrast, narrow self-interest cannot explain why travellers might leave tips in restaurants located along interstate highways. Because it is unlikely that they will ever visit these restaurants again, their failure to tip cannot affect the quality of service they expect to receive in the future. So it is hard to escape the conclusion that concerns about fairness must be implicated when diners tip on the road. Of course, merely to assert the existence of a sense of fairness does not really explain why people often set aside concern for narrow self-interest. It simply raises the more fundamental question of why people have a sense of fairness in the first place. It is this question I will discuss.

Cooperative Behavior↗

Antinociceptive effect of antisense oligonucleotides against the vanilloid receptor VR1/TRPV1.

To examine the role of the vanilloid receptor TRPV1 in neuropathic pain, we assessed the effects of the receptor antagonist thioxo-BCTC and antisense oligonucleotides against the TRPV1 mRNA in a rat model of spinal nerve ligation. In order to identify accessible sites on the mRNA of TRPV1, the RNase H assay was used, leading to the successful identification of binding sites for antisense oligonucleotides. Cotransfection studies using Cos-7 cells were employed to identify the most effective antisense oligonucleotide efficiently inhibiting the expression of a fusion protein consisting of TRPV1 and the green fluorescent protein in a specific and concentration-dependent manner. In an in vivo rat model of spinal nerve ligation, intravenous application of the TRPV1 antagonist thioxo-BCTC reduced mechanical hypersensitivity yielding an ED(50) value of 10.6mg/kg. Intrathecal administration of the antisense oligonucleotide against TRPV1, but not the mismatch oligonucleotide or a vehicle control, reduced mechanical hypersensitivity in rats with spinal nerve ligation in a similar manner. Immunohistochemical analysis revealed neuropathy- and antisense-associated regulation of TRPV1 protein expression in spinal cord and dorsal root ganglia. Our data demonstrate comparative analgesic effects of a TRPV1 anatagonist and a rationally designed TRPV1 antisense oligonucleotide in a spinal nerve ligation model of neuropathic pain and thus, lend support to the validation of TRPV1 as a promising target for the treatment of neuropathic pain.

Analgesics↗

Silencing of vanilloid receptor TRPV1 by RNAi reduces neuropathic and visceral pain in vivo.

RNA interference (RNAi) has proven to be a powerful technique to study the function of genes by producing knock-down phenotypes. Here, we report that intrathecal injection of an siRNA against the transient receptor potential vanilloid receptor 1 (TRPV1) reduced cold allodynia of mononeuropathic rats by more than 50% over a time period of approximately 5 days. A second siRNA targeted to a different region of the TRPV1 gene was employed and confirmed the analgesic action of a TRPV1 knock-down. Furthermore, siRNA treatment diminished spontaneous visceral pain behavior induced by capsaicin application to the rectum of mice. The analgesic effect of siRNA-mediated knockdown of TRPV1 in the visceral pain model was comparable to that of the low-molecular weight receptor antagonist BCTC. Our data demonstrate that TRPV1 antagonists, including TRPV1 siRNAs, have potential in the treatment of both, neuropathic and visceral pain.

Animals↗

Respiratory effects of inhalation exposure among workers during the clean-up effort at the World Trade Center disaster site.

During December 2001 we conducted a field study of 183 clean-up and recovery workers at the World Trade Center (WTC) disaster site to assess respiratory health effects potentially resulting from their work at the site. On site, we administered a respiratory health questionnaire designed to assess upper respiratory symptoms and lower respiratory symptoms, including cough, phlegm, and wheeze, as well as indices of exposure, including number of days worked at the site and job category. Spirometry was conducted for 175 workers. Sixty-five percent of the workers surveyed arrived at the site without lower respiratory symptoms. Of this group, 34% developed cough, 24% developed phlegm, and 19% developed wheeze. Prevalence rates of these symptoms were related to the number of days spent working at the WTC, but not job category. The mean percentage predicted FEV(1) and FVC were 6% and 5% lower, respectively, for workers who developed new lower respiratory symptoms compared to those who remained symptom free. While the development of new wheeze suggested the presence of airway obstruction, the near-normal distribution of age-adjusted FEV(1)/FVC ratios suggested that the degree of obstruction was mild. The prevalence rates of upper airway symptoms (nasal congestion, sore throat, hoarse throat) exceeded those of lower respiratory symptoms, however, it was not determined whether symptoms pre-dated arrival at the WTC site.

Adult↗

Natural history and risk stratification of arrhythmogenic right ventricular dysplasia/cardiomyopathy.

BACKGROUND: Management of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is complicated by the incomplete information on the natural history of the disease and by the lack of risk stratification for cardiovascular death. The aim of the study was the identification of risk factors related to long-term prognosis. METHODS AND RESULTS: Data were collected from 130 patients (100 men; age at onset of symptoms, 31.8+/-14.4 years) from a tertiary center between 1977 and 2000 who fulfilled the international standardized diagnostic criteria for ARVD/C. Risk factors for cardiovascular death were determined by a logistic regression model. After a mean follow-up of 8.1+/-7.8 years, 24 deaths were recorded, with a mean age at death of 54+/-19 years (annual mortality rate, 2.3%). There were 21 deaths with a cardiovascular origin (progressive heart failure for 14 patients and sudden death for the remaining 7 patients). All patients who died had a history of ventricular tachycardia. Multivariate analysis showed that after adjustment for sex, history of syncope, chest pain, inaugural ventricular tachycardia, recurrence of ventricular tachycardia, and QRS dispersion, clinical signs of right ventricular failure and left ventricular dysfunction both remained independently associated with cardiovascular mortality. The combined presence of one of these risk factors and ventricular tachycardia identifies high-risk subjects for cardiovascular mortality, whereas patients without ventricular tachycardia displayed the best prognosis. CONCLUSIONS: The information on the natural history of patients with ARVD allowed us to identify risks factors for cardiovascular mortality. An analysis of a large international registry is needed to refine these results.

Adolescent↗

Angiographic right and left ventricular function in arrhythmogenic right ventricular dysplasia.

We prospectively documented right ventricular (RV) and left ventricular (LV) volumes and ejection fractions in a large series of patients with arrhythmogenic RV dysplasia/cardiomyopathy (ARVD/C). Eighty-five patients with ARVD/C and 11 controls underwent 2 successive orthogonal right and left monoplane x-ray-digitized cineangiographies. Volumes were calculated using the hemielliptical RV and ellipsoidal LV models. All controls and 58 of 85 patients (ARVD/C-I) had a RV ejection fraction > or =35% and 27 patients had a RV ejection fraction <35% (ARVD/C-II). Tricuspid annulus plane systolic excursion (TAPSE) was lower in ARVD/C-II than in ARVD/C-I patients (6 +/- 3 vs 14 +/- 3 mm) and controls (16 +/- 2 mm) (each p <0.001). In patients with ARVD/C, TAPSE was positively related to RV ejection fraction (r = 0.79) and to crista supraventricularis shortening (r = 0.81) (each p <0.001). Sensitivity and specificity of TAPSE <12 mm in identifying patients with RV ejection fraction <35% were 96% and 78%, respectively. LV ejection fraction was > or =50% in 68 patients, 40% to 49% in 10, and <40% in 7. Diffuse RV outflow tract aneurysm was observed in 9 patients, all belonging to ARVD/C-II, and this sign identified patients with LV ejection fraction <40% with 86% sensitivity and 96% specificity. In conclusion, 68% of ARVD/C patients had normal RV ejection fraction and RV volumes, and 80% of ARVD/C patients had normal LV ejection fraction. Decreased TAPSE <12 mm and a diffuse RV outflow tract aneurysm were sensitive and specific indicators of RV ejection fraction <35% and LV ejection fraction <40%, respectively.

Adult↗

[Narrow QRS tachycardia].

Narrow QRS tachycardia are supraventricular tachycardia, atrial tachycardia or junctional tachycardia. The diagnosis is done with the ECG, after identification of atrial activation, eventually after vagal manoeuvres, and transoesophageal recordings. DC Choc, atrial pacing, or antiarrhythmic drugs can do interruption. All atrial tachycardia must be anticoagulated prior regularisation. There is seldom an emergency for regularisation, as drugs can always slow the ventricular rate down. Prevention of relapses uses oral antiarrhythmic drugs, sometimes pacing. Most of these tachycardia can be cured by catheter ablation, essentially flutter and junctional tachycardia.

Electrocardiography↗

Medical acupuncture in Germany: patterns of consumerism among physicians and patients.

Since the (re) emergence of heterodox medicine across the Western world, there have been numerous interpretations of this phenomenon by the social sciences. Heterodox patients were said to be active consumers holding postmodern values, while heterodox physicians were described as heretics. Medical doctors taking up heterodox medicine were criticised for acting in their own financial interests. To examine these notions, we selected the most prominent heterodox mode of treatment in the German healthcare system: acupuncture. Twenty-six semi-structured interviews with medical acupuncturists and their patients were conducted. On the physicians' side, we analyse their styles of practice. To what extent is acupuncture incorporated into biomedical models? Were there any doctors who completely converted to Chinese ideas about health and illness? The patients' activities before and during treatment are addressed. What made them choose acupuncture? How thoroughly did- and do- they collect information on heterodox treatment? The patients' perception of their relationship with their physicians and the decision-making processes during the consultations are also examined. Finally, we argue that while some modes of heterodox medicine resemble parallel forms of general practice, acupuncture tends to become a medical speciality in which physicians tailor their practice to the individual patient's (perceived) demands. From the patients' perspectives, a passive rather than active form of consumerism emerges, involving ideas on medical services that closely correspond to classical modernity.

Acupuncture↗

Mapping and ablation of ventricular fibrillation associated with long-QT and Brugada syndromes.

BACKGROUND: The long-QT and Brugada syndromes are important substrates of malignant ventricular arrhythmia. The feasibility of mapping and ablation of ventricular arrhythmias in these conditions has not been reported. METHODS AND RESULTS: Seven patients (4 men; age, 38+/-7 years; 4 with long-QT and 3 with Brugada syndrome) with episodes of ventricular fibrillation or polymorphic ventricular tachycardia and frequent isolated or repetitive premature beats were studied. These premature beats were observed to trigger ventricular arrhythmias and were localized by mapping the earliest endocardial activity. In 4 patients, premature beats originated from the peripheral right (1 Brugada) or left (3 long-QT) Purkinje conducting system and were associated with variable Purkinje-to-muscle conduction times (30 to 110 ms). In the remaining 3 patients, premature beats originated from the right ventricular outflow tract, being 25 to 40 ms ahead of the QRS. The accuracy of mapping was confirmed by acute elimination of premature beats after 12+/-6 minutes of radiofrequency applications. During a follow-up of 17+/-17 months using ambulatory monitoring and defibrillator memory interrogation, no patients had recurrence of symptomatic ventricular arrhythmia but 1 had persistent premature beats. CONCLUSIONS: Triggers from the Purkinje arborization or the right ventricular outflow tract have a crucial role in initiating ventricular fibrillation associated with the long-QT and Brugada syndromes. These can be eliminated by focal radiofrequency ablation.

Adult↗

Effective long-term left atrial pacing using regular screw-in leads implanted within the coronary sinus.

Passive-fixation leads positioned inside the coronary sinus (CS) have been found to be effective in LA pacing and sensing, but their use is limited by a high incidence of early and late dislodgment. Since anatomic studies have shown that the proximal part of the CS is surrounded by a relatively thick musculature, the feasibility, safety, and efficacy of acute and chronic coronary sinus pacing via regular screw-in leads positioned within the first centimeters of the CS were evaluated as compared to passive-fixation leads. Thirty-three patients (21 men, age 62 +/- 10 years) underwent dual chamber pacemaker implantation with LA pacing obtained via passive-fixation leads (7 patients) or regular screw-in leads (26 patients). The former approach was prematurely abandoned because of a high rate of acute and late lead dislodgment (42%). The chronic pacing threshold was 1.7 +/- 1.0 V at 0.67-ms pulse width and 1.47 +/- 1.3 V at 0.5-ms pulse width for passive- and active-fixation leads, respectively. In the CS active-fixation lead group, no postoperative pericardial effusion, CS lead dislodgment, nor diaphragmatic stimulation were observed. In this last group, steroid eluting leads (14 patients) have a statistically lower pacing threshold than noneluting steroid leads (12 patients) (0.88 +/- 0.23 vs 2.29 +/- 1.68 V, P = 0.011) at long-term follow-up. The use of regular screw-in leads implanted within the CS allows effective and safe long-term LA pacing without risk of dislodgment.

Atrial Function, Left↗

Cycle length-dependent repolarization changes during atrial fibrillation in the Brugada syndrome.

This is a case report of a patient with Brugada syndrome who developed paroxysmal atrial fibrillation. During the episode, beat-to-beat changes in ventricular repolarization were observed. These changes were a paradoxical ST-segment alteration after a short-coupled ventricular beat. These findings, not reported before, may be helpful for the diagnosis of this syndrome.

Atrial Fibrillation↗

Measurement practices: methods for developing content-valid student examinations.

Measurement experts generally agree that a systematic approach to test construction will probably result in an instrument with sound psychometric properties. One fundamental method is called the blueprint approach to test construction. A test blueprint is a tool used in the process for generating content-valid exams by linking the subject matter delivered during instruction and the items appearing on the test. Unfortunately, this procedure as well as other educational measurement practices is often overlooked A survey of curriculum administrators at 144 United States and international medical schools was conducted to assess the importance and prevalence of test blueprinting in their school. Although most found test blueprinting to be very important, few require the practice. The purpose of this paper is to review the fundamental principals associated with achieving a high level of content validity when developing tests for students. The short-term efforts necessary to develop and integrate measurement theory into practice will lead to long-term gains for students, faculty and academic institutions.

Administrative Personnel↗

Unstable heart rate and temperature regulation predict mortality in AKR/J mice.

Elderly populations face greater risks of mortality when exposed to changes in environmental stress. The purpose of the following study was to develop an age-dependent susceptibility model that achieved the following three goals: 1) to operationally define homeostasis by assessing the stability and periodicity in physical activity, heart rate (HR), and deep body temperature (T(db)), 2) to specify alterations in activity, HR, and T(db) regulation that signal imminent death, and 3) to test the hypothesis that the decay in homeostasis associated with imminent death incorporates the coincident disintegration of multiple physiological systems. To achieve these goals, the circadian regulation of activity, HR, and T(db) was assessed using radiotelemeters implanted in AKR/J (n = 17) inbred mice at approximately 190 days of age. During a 12:12-h light-dark cycle, weekly measurements were obtained at 30-min intervals for 48-h periods until each animal's natural death. The average (+/-SE) life span of surgically treated animals did not differ from untreated controls (319 +/- 12 vs. 319 +/- 14 days). Cardiac and thermal stability were characterized by a circadian periodicity, which oscillated around stable daily averages of 640 +/- 14 beats/min in HR and 36.6 +/- 0.1 degrees C in T(db). Stable HR and T(db) responses were compared with extreme conditions 3 days before death, during which a disintegration of circadian periodicity was coincident with a fall in the daily average HR and T(db) of approximately 29 and approximately 13% lower (i.e., 456 +/- 22 beats/min and 31.7 +/- 0.6 degrees C), respectively. The results further suggested that multiple predictors of cardiac and thermal instability in AK mice, including significant bradycardia, hypothermia, and a loss of circadian periodicity, forecast life span 5-6 wk before expiration.

Animals↗