Dobutamine magnetic resonance imaging as a predictor of myocardial functional recovery after revascularisation

OBJECTIVE—To assess the use of dobutamine magnetic resonance imaging (MRI) as a preoperative predictor of myocardial functional recovery after revascularisation, comparing wall motion and radial wall thickening analyses by observer and semi-automated edge detection.
PATIENTS—25 men with multivessel coronary disease and resting wall motion abnormalities were studied with preoperative rest and stress MRI.
MAIN OUTCOME MEASURES—Observer analysis for radial wall thickening was compared with a normal range, while wall motion analysis used a standard four point scale. Semi-automated analysis was performed using an edge detection algorithm. Segments displaying either improved or worsened thickening or motion with dobutamine were considered viable. Postoperative rest images were performed 3-6 months after coronary artery bypass grafting (CABG) for comparison.
RESULTS—For observer analysis the values for sensitivity and specificity were 50% and 72% for wall motion, with respective values of 50% and 68% for thickening. With semi-automated edge detection the figures for motion were 60% and 73%, with corresponding values of 79% and 58% for thickening. Combining thickening and motion for the semi-automated method to describe any change in segmental function yielded a sensitivity of 71% and specificity of 70%.
CONCLUSIONS—Dobutamine MRI is a reasonably good predictor of myocardial functional recovery after CABG. The use of semi-automated edge detection analysis improved results.


Keywords: dobutamine; magnetic resonance imaging myocardial viability; coronary artery bypass grafting     

Enhanced purification and production of Müllerian inhibiting substance for therapeutic applications

It is almost 60 years since Prof. Alfred Jost reported the seminal observations regarding Müllerian inhibiting substance (MIS). His experiments clearly showed that a testicular product other than testosterone, a Müllerian inhibitor, was responsible for Müllerian duct regression. Twenty-five years later Dr. Picon established an organ culture assay which paved the way for the initial studies into the biochemistry and biology of Müllerian inhibiting substance, also known as Anti-Müllerian hormone (AMH), undertaken first in Dr. Nathalie Josso's Laboratory in Paris then in our own laboratory in Boston. Purification of MIS led to cloning the human gene and production of recombinant human (rhMIS). MIS is a 140 kDa glycoprotein homodimer which is activated by a biosynthetic protease, cleaving MIS into an aminoterminus (110 kDa) and a carboxyterminus (25 kDa). The latter domain is sufficient for biological activities. MIS functions by interacting with two receptors; a type II binds the hormone and at type I that initiates downstream signaling. The MIS type II receptor has been cloned and functionally confirmed as distinct from that of other members of the TGFbeta superfamily. MIS can employ a number of type I receptors (ALK2, ALK3, ALK6) and BMP receptor specific SMADS 1, 5, and 8 in various tissue specific contexts. Cell lines derived from human ovarian, breast, and prostate tumors, and from rodent Leydig cell tumors, which respond to MIS in growth inhibition assays, all express the MIS type II receptor. A variety of signal transduction pathways are associated with the grown inhibition mediated by MIS. For example, breast and prostate cancer cell lines use a MIS-mediated NFkappaB pathway leading to G1 arrest and apoptosis. The ovarian cancer cell lines employ a pathway which enhances p16, modulates the E2Fs, and induces apoptosis. These signal transduction events can establish new rational treatment strategies to complement the growth inhibitory effects mediated by MIS. These combination strategies are being tested in vitro, and where appropriate will be tested in vivo using the highly purified MIS preparations, prior to use in early human clinical trials.     

The influence of social evaluation on cerebral cortical activity and motor performance: A study of “Real-Life” competition

Motor performance in a social evaluative environment was examined in participants (N = 19) who completed a pistol shooting task under both performance-alone (PA) and competitive (C) conditions. Electroencephalographic (EEG), autonomic, and psychoendocrine activity were recorded in addition to kinematic measures of the aiming behavior. State anxiety, heart rate, and cortisol were modestly elevated during C and accompanied by relative desynchrony of high-alpha power, increased cortico-cortical communication between motor and non-motor regions, and degradation of the fluency of aiming trajectory, but maintenance of performance outcome (i.e., score). The findings reveal that performance in a complex social-evaluative environment characterized by competition results in elevated cortical activity beyond that essentially required for motor performance that translated as less efficient motor behavior.     

Eating disorder diagnosis and the female athlete: A longitudinal analysis from college sport to retirement

ObjectivesFemale athletes experience eating disorders (EDs) at clinical, and subclinical, levels; most studies have determined point-prevalence rates through cross-sectional methodologies. To date, few studies have examined the long-term stability of EDs in female athletes; none extend into retirement.DesignA longitudinal investigation of ED classification (i.e., Clinical ED, Subclinical ED, Healthy) and weight control behaviors (e.g., vomiting, laxative use) from when athletes actively competed (T1) into their retirement (T2).MethodsParticipants included U.S. female athletes (N = 193) who were collegiate competitors (T1) and eventually were retired from their collegiate sports six years later (T2).ResultsAt T2, athletes were classified as Healthy (69.9%), Subclinical ED (26.9%), and Clinical ED (3.1%). Overall percentage of Subclinical EDs increased from 18.7% (T1) to 26.9% (T2); 52.8% of T1 Subclinical ED athletes continued to meet criteria for either Subclinical or Clinical ED at T2. Of the 13 Clinical ED athletes at T1, six (46.2%) continued to meet criteria for either a subclinical or clinical ED at T2. Though exercising (2+ hours/day; n = 8, 4.1%) and dieting/fasting (4+ times/year; n = 14, 7.3%) were the most frequently used weight control behaviors at T2, rates were substantially lower than at T1.ConclusionsRetirement does not result in immediate remittance of eating concerns among female athletes; many continue or develop Subclinical and Clinical ED symptoms. Thus, addressing healthy body image and nutrition when athletes are competing is imperative to assist prevention and intervention efforts that may alleviate ED symptoms as athletes transition from sport.     

The epidemiology of hepatitis C in a UK health regional population of 5.12 million

BACKGROUND: The epidemiology and natural history of hepatitis C virus (HCV) infection in the UK are uncertain. Previous reports are from small or selected populations such as blood donors or tertiary referral centres. AIMS: To study the epidemiology and natural history of HCV infection. METHODS: Prospective study incorporating five centres within the Trent region. Patients were managed and followed up according to a commonly agreed protocol. SUBJECTS: A total of 1128 HCV positive patients. Patients with haemophilia, human immunodeficiency virus, and chronic renal failure were excluded. RESULTS: Between September 1991 and December 1998, 2546 anti-HCV positive patients were identified of whom 1128 (44%) were enrolled in the cohort. A risk factor(s) for infection was identified in 93.4% of patients who completed the questionnaire; 81% of patients were HCV RNA positive. A total of 397 initial liver biopsies were scored by a single pathologist. These showed a correlation between high alcohol intake and fibrosis score. Multivariate analysis showed fibrosis to be associated with age over 40, past evidence of hepatitis B virus infection, and higher necroinflammatory grade but not with sex, viral genotype, maximum known alcohol intake, estimated duration of infection, or mode of transmission. Twelve (7.8%) of 153 patients who received interferon therapy had sustained serum virus clearance. Sixty six patients have died during the follow up period, 31 with a liver related cause of death. This represents a considerable excess over the expected death rate for a cohort of this age and sex distribution. CONCLUSIONS: HCV infection is an emerging health problem in the Trent region. Identifying risk factors for infection and disease severity will enhance understanding and facilitate improved intervention. An excess mortality in infected individuals is already evident in this unselected cohort.