Exercise Intolerance in Patients With Heart Failure: JACC State-of-the-Art Review

Exercise intolerance is the cardinal symptom of heart failure (HF) and is of crucial relevance, because it is associated with a poor quality of life and increased mortality. While impaired cardiac reserve is considered to be central in HF, reduced exercise and functional capacity are the result of key patient characteristics and multisystem dysfunction, including aging, impaired pulmonary reserve, as well as peripheral and respiratory skeletal muscle dysfunction. We herein review the different modalities to quantify exercise intolerance, the pathophysiology of HF, and comorbid conditions as they lead to reductions in exercise and functional capacity, highlighting the fact that distinct causes may coexist and variably contribute to exercise intolerance in patients with HF.     

Experimental intracerebral hemorrhage: avoiding pitfalls in translational research

Intracerebral hemorrhage (ICH) has the highest mortality of all stroke subtypes, yet treatments are mainly limited to supportive management, and surgery remains controversial. Despite significant advances in our understanding of ICH pathophysiology, we still lack preclinical models that accurately replicate the underlying mechanisms of injury. Current experimental ICH models (including autologous blood and collagenase injection) simulate different aspects of ICH-mediated injury but lack some features of the clinical condition. Newly developed models, notably hypertension- and oral anticoagulant therapy-associated ICH models, offer added benefits but further study is needed to fully validate them. Here, we describe and discuss current approaches to experimental ICH, with suggestions for changes in how this condition is studied in the laboratory. Although advances in imaging over the past few decades have allowed greater insight into clinical ICH, there remains an important role for experimental models in furthering our understanding of the basic pathophysiologic processes underlying ICH, provided limitations of animal models are borne in mind. Owing to differences in existing models and the failed translation of benefits in experimental ICH to clinical practice, putative neuroprotectants should be trialed in multiple models using both histological and functional outcomes until a more accurate model of ICH is developed.     

Disciplinary discourses: rates of cesarean section explained by medicine, midwifery, and feminism

In the context of international concern about increasing rates of cesarean sections, we used discourse analysis to examine explanations arising from feminism and the disciplines of medicine and midwifery, and found that each was positioned differently in relation to the rising rates. Medical discourses asserted that doctors are authorities on birth and that, although cesareans are sometimes medically necessary, women recklessly choose unnecessary cesareans against medical advice. Midwifery discourses portrayed medicine as paternalistic toward both women and midwifery, and feminist discourses situated birth and women's bodies in the context of a patriarchally structured society. The findings illustrate the complex ways in which this intervention in birth is discursively constructed, and demonstrate its significance as a site of disciplinary conflict.     

Saviours and satyrs: ambivalence in narrative meanings of sperm provision

This paper reports on the complex representations of sperm providers in the narratives of donors, recipients and offspring involved in donor‐assisted conception. Eighty‐seven volunteers from Australia, Canada, UK, USA and Argentina participated in qualitative narrative research. Sperm provision was perceived to be publicly represented as sexualized, provoking both disgust and hilarity; this is interpreted as arising from its association with masturbation and the metaphorical representation of the donor sperm as cuckolding the recipient's husband. Recipients' representations of providers were found to mix gratitude with resentment, embarrassment, and anxiety; their constructions are strongly influenced by the position of the social father. The complex representation of the provider as a genetic father is considered: providers can be seen as threatening the integrity of parents if they become involved in the life of their offspring and abandoning their offspring to confusion and despair if they do not. The research demonstrates that, in spite of its relative frequency and familiarity, donor insemination is still represented ambivalently, including by those who may be said to benefit from it.     

Experience of the first pelvic examination.

OBJECTIVES: To analyze women's experiences of the first pelvic examination and identify positive and negative components. To learn lessons, and build on and incorporate the positive components into a model of good clinical practice. METHOD: The open, cross-sectional study was carried out in community family planning and young persons clinics. A self-administered questionnaire was offered to all women under 25 years of age who attended a family planning or young persons clinic during the study period. The questionnaire was constructed to determine how experience compared with expectations and which components showed a significant trend towards a positive or negative effect. It also aimed to find what women considered to be important aspects of an internal examination. RESULTS: A total of 167 evaluable questionnaires were completed in which experience of the first pelvic examination was reported from family planning clinics (41%), general practice (39%) and hospital/genitourinary medicine faculties (20%). These first pelvic examinations occurred at a mean age of 17.3 years (range 11-23 years). Significant trends of a positive experience were found when the examination was conducted by a female doctor (p = 0.02), when it was conducted in a family planning clinic as opposed to general practice (p = 0.04), after permission was sought (p = 0.001) and with increasing age at first examination (Mann-Whitney, p = 0.003). There were no significant differences in outcome with offer of, or presence of, a chaperone. CONCLUSIONS: A friendly, female doctor who seeks permission before the examination, which should be uninterrupted, were considered to be important aspects for an internal examination.     

Transmission of hepatitis C virus by organ transplantation.

BACKGROUND. Liver disease is a frequent and major complication after organ transplantation. We sought to determine whether hepatitis C virus (HCV) is transmitted by organ transplantation and whether it causes post-transplantation liver disease. METHODS. Serum samples from all cadaver organ donors to the New England Organ Bank between 1986 and 1990 were screened retrospectively for antibodies to HCV (anti-HCV) by enzyme-linked immunosorbent assay (ELISA). We reviewed the hospital records of all recipients of organs from anti-HCV-positive donors for evidence of liver disease. Serum samples from recipients obtained before transplantation and during follow-up were analyzed for anti-HCV. RESULTS. Of 716 organ donors, 13 (1.8 percent) were positive for anti-HCV. Their organs (19 kidneys, 6 hearts, and 4 livers) went to 29 recipients. Non-A, non-B hepatitis developed after transplantation in 14 of the 29 (48 percent), for a prevalence 7.4 times the 6.5 percent prevalence after transplantation from untested donors that was previously reported by two institutions in the organ bank (P less than 0.0001). The liver disease began a mean of 3.8 months after transplantation and became chronic in 12 patients; the other 2 had subfulminant hepatic failure. Liver disease was more frequent in the patients who had received antilymphocyte preparations (P = 0.04). HCV was the cause of the post-transplantation liver disease in 12 of the 13 recipients (92 percent) for whom serum samples were available. Anti-HCV was detected by ELISA in eight and enzyme immunoassay in one; in three others, HCV RNA was detected by polymerase chain reaction in serum samples obtained after transplantation. CONCLUSIONS. Organ transplantation can transmit hepatitis C. This raises serious questions about the continued acceptance of organs from donors positive for anti-HCV.     

Cocaine use increases [HWIN 35428 binding sites in human striatum

Animal studies suggest that chronic cocaine exposure may increase the function and/or synthesis of the dopamine transporter (DAT) under certain conditions, but the literature is complex. In order to test the hypothesis that cocaine exposure alters the DAT in humans, preliminary studies were done characterizing [³HWIN 35428 binding in human striatum from normal controls. Following these experiments, the effects of chronic cocaine were examined in post mortem striatal specimens from 7 cocaine users and 7 controls matched for age and post mortem interval, employing quantitative autoradiography. Initial saturation experiments indicated that a one-site model was preferred with aK_d of11±4nM. [³HWIN 35420 binding was then examined in cocaine users and controls at 0.5, 5, 10, and 50 nM radioligand concentrations. At each concentration of [³HWIN 35420, optical densities for cocaine-exposed subjects were increased in caudate, putamen, and accumbens. The results suggest that total numbers of binding sites were increased in cocaine users. Based on the present and previous results, it appears that the regulation of the DAT is fairly plastic, and is highly sensitive to cocaine dosing regimes and withdrawal intervals. Chronic adaptations induced by cocaine in the DAT could contribute to the symptoms of binging, withdrawal depression, and/or craving.