Background Cancer patients are at risk of developing blood clots in their veins - venous thromboembolism - which often takes the form of a pulmonary embolism or deep vein thrombosis. The risk increases with advanced disease. Evidence based treatment is low molecular weight heparin by daily subcutaneous injection. The aim of this research is to explore the barriers for doctors in the UK when diagnosing and treating advanced cancer patients with VTE. Method Qualitative, in-depth interview study with 45 (...) doctors. Doctors were from three specialties: oncology, palliative medicine and general practice, with a mixture of senior and junior staff. Framework analysis was used. Results Doctors opinions as to whether LMWH treatment was ethically appropriate for patients who were symptomatic from VTE but at end of life existed on a shifting continuum, largely influenced by patient prognosis. A lack of immediate benefit coupled with the discomfort of a daily injection had influenced some doctors not to prescribe LMWH. The point at which LMWH injections should be stopped in patients at the end of life was ambiguous_._ Some perceived ‘overcaution’ in their own and other clinicians’ treatment of patients_._ Viewpoints were divergent on whether dying of a PE was considered a “good way to go”. The interventionalism and ethos of palliative medicine was discussed. Conclusions Decisions are difficult for doctors to make regarding LMWH treatment for advanced cancer patients with VTE. Treatment for this patient group is bounded to the doctors own moral and ethical frameworks. (shrink)

Background: Cancer patients are at risk of developing blood clots in their veins - venous thromboembolism(VTE) - which often takes the form of a pulmonary embolism or deep vein thrombosis. Therisk increases with advanced disease. Evidence based treatment is low molecular weightheparin (LMWH) by daily subcutaneous injection. The aim of this research is to explore thebarriers for doctors in the UK when diagnosing and treating advanced cancer patients withVTE.MethodQualitative, in-depth interview study with 45 doctors (30 across Yorkshire, England (...) and 15across South Wales). Doctors were from three specialties: oncology, palliative medicine andgeneral practice, with a mixture of senior and junior staff. Framework analysis was used. Results: Doctors opinions as to whether LMWH treatment was ethically appropriate for patients whowere symptomatic from VTE but at end of life existed on a shifting continuum, largelyinfluenced by patient prognosis. A lack of immediate benefit coupled with the discomfort of adaily injection had influenced some doctors not to prescribe LMWH. The point at whichLMWH injections should be stopped in patients at the end of life was ambiguous. Someperceived overcaution in their own and other clinicians treatment of patients. Viewpointswere divergent on whether dying of a PE was considered a "good way to go". Theinterventionalism and ethos of palliative medicine was discussed. Conclusions: Decisions are difficult for doctors to make regarding LMWH treatment for advanced cancerpatients with VTE. Treatment for this patient group is bounded to the doctors own moral andethical frameworks. (shrink)

Focusing on the controversial birth control pills Yaz and Yasmin, this article explores how debates about the safety of these drugs have materialized in risk evaluations and the management of technological risk. Drawing on in-depth interviews with stakeholders and content analysis of legal, medical, and regulatory documents, I highlight how professional contraceptive risk assessment is characterized by systemic uncertainty and doubt, resulting in increased responsibility for users themselves to manage the drugs’ potentially increased risks of venous thromboembolism. The (...) analysis centers on three key areas in the assessment process that denote disagreement: risk measurement in postmarket surveillance data, the distinctiveness of the drugs’ benefits when compared to other contraceptive technologies, and the weighing of the risks and benefits against each other. While professionals negotiate uncertainty both in epidemiological research and in clinical practice, users are constructed as agents who should manage risk individually. Such processes are underlined by a diffusion of responsibility in the systemic management of contraceptive risk. This article suggests, more broadly, that medical technologies can be conceptualized as artifacts that are instrumental in the dispersion of risks. (shrink)

This article deals with physico-mathematical approaches to anatomy in post-Harveyan physiology. But rather than looking at questions of iatromechanics and animal locomotion, which often attracted this approach, I look at the problem of how blood returned to the heart – a part of the circulation today known as venous return but poorly researched in the early modern period. I follow the venous return mechanisms proposed by lesser-known authors in the mechanization of anatomy, such as Jean Pecquet (1622–1674) and (...) Nicolaus Steno (1638–1686), alongside the more famous Giovanni Alfonso Borelli (1608–1679). Their mechanisms differed only in small details. Yet, these minor differences highlight significant aspects of the mechanization of the life sciences in the seventeenth century. First, they relied more on observations than hitherto acknowledged, even if only indirectly. Second, their mechanisms drew more from the physico-mathematical disciplines than from the trending corpuscularian philosophies of their time. Finally, these mechanisms led to a more accurate understanding of the circulation that remains valid today, thus revealing their cognitive benefits. In short, through the single problem of how blood returned to the heart, this article portrays the increasing complexity of anatomy in the early modern period. (shrink)

Alterations in dural venous sinus hemodynamics have recently been suggested as the major contributing factors in venous pulsatile tinnitus. Nevertheless, little is known about the association between real-time alterations in hemodynamics and the subjective perception of venous PT. This study aimed to investigate the hydroacoustic correlations among diverticular vortices, mainstream sinus flow, and PT using various Doppler ultrasound techniques. Nineteen venous PT patients with protrusive diverticulum were recruited. The mainstream sinus and diverticular hemodynamics before and after (...) ipsilateral internal jugular vein compression were investigated using an innovative retroauricular color-coded Doppler method to examine the correlation between the disappearance of PT and hemodynamic alterations. To reveal the hydroacoustic characteristics of disparate segments of venous return, a computational fluid dynamics technique combined with the transcranial color-coded Doppler method was performed. When the ipsilateral IJV was compressed, PT disappeared, as the mean velocity of mainstream sinus flow and diverticular vortex decreased by 51.2 and 50.6%, respectively. The vortex inside the diverticulum persisted in 18 of 19 subjects. The CFD simulation showed that the flow amplitude generated inside the transverse–sigmoid sinus was segmental, and the largest flow amplitude difference was 20.5 dB. The difference in flow amplitude between the mainstream sinus flow and the diverticular flow was less than 1 dB. In conclusion, the sensation of PT is closely associated with the flow of kinetic energy rather than the formation of a vortex, whereby the amplitude of PT is correlated to the magnitude of the flow velocity and pressure gradient. Additionally, the range of velocity reduction revealed by the RCCD method may serve as a presurgical individual baseline curative marker that may potentially optimize the surgical outcomes. (shrink)

Chronically ill conditions are particularly difficult to manage because of their impact both on the social and on the corporal sphere to such an extent as to involve a series of problems that negatively alter the quality of life of affected patients. Chronicity has also a considerable ef-fect on social capital. In the current literature, it is known that social capital may contribute to a range of advantages to people health. Chronic Venous Disease (CVD) includes several pathologi-cal alterations of (...) the venous system of the lower limbs that cause a wide range of symptoms and signs. The aim of this study is to explore, with a qualitative approach, the dynamics of social cap-ital within people's experience of CVD and describe the roles of family and friends and the health care system. The method used is based on face-to-face semistructured interviews was performed, following the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. Six-teen patients were included: 11 women and 5 men. The results obtained are completely in line with the current literature, which shows a certain difficulty in terms of daily activities, pain management; work-related difficulties; non-coverage of healthcare costs for medications and drugs prescribed. In the context of social capital, the bonding social capital of the patients inter-viewed was more positively perceived in the role of CVD management than by the patients' fami-lies. Another interesting result concerns the total absence of knowledge of patient associations with CVD. Thus, alongside the biographical destruction that CVD entails, there is evidence of the scarce relevance and presence of health policies capable of improving the quality of life of these people not only from a social and medical point of view but also from an economic point of view. (shrink)

This paper will examine a sample case encountered by ambulance staff in the context of the basic principles of medical ethics.An accident takes place on an intercity highway. Ambulance staff pick up the injured driver and medical intervention is initiated. The driver suffers from a severe stomach ache, which is also affecting his back. Evaluating the patient, the ambulance doctor suspects that he might be experiencing internal bleeding. For this reason, venous access, in the doctor's opinion, should be achieved (...) and the patient should be quickly started on an intravenous serum. The patient, however, who has so far kept his silence, objects to the administration of the serum. The day this is taking place is within the month of Ramadan and the patient is fasting. The patient states that he is fasting and that his fast will be broken and his religious practice disrupted in the event that the serum is administered. The ambulance doctor informs him that his condition is life-threatening and that the serum must be administered immediately. The patient now takes a more vehement stand. ‘If I am to die, I want to die while I am fasting. Today is Friday and I have always wanted to die on such a holy day,’ he says. The ambulance physician has little time to decide. How should the patient be treated? Which type of behaviour will create the least erosion of his values? (shrink)

The rare but severe cerebral venous thrombosis occurring in some AstraZeneca vaccine recipients has prompted some governments to suspend part of their COVID-19 vaccination programmes. Such suspensions have faced various challenges from both scientific and ethical angles. Most of the criticisms against such suspensions follow a consequentialist approach, arguing that the suspension will lead to more harm than benefits. In this paper, I propose a rights-based argument against the suspension of the vaccine rollouts amid this highly time-sensitive combat of (...) COVID-19. I argue that by suspending a vaccine rollout, a government infringes people's right to take the risks they deem worth taking for their health. I also consider four potential objections to my argument and explain why none of them undermines my argument. (shrink)

A tree‐like hierarchical branching structure is present in many biological systems, such as the kidney, lung, mammary gland, and blood vessels. Most of these organs form through branching morphogenesis, where outward growth results in smaller and smaller branches. However, the blood vasculature is unique in that it exists as two trees (arterial and venous) connected at their tips. Obtaining this organization might therefore require unique developmental mechanisms. As reviewed here, recent data indicate that arterial trees often form in reverse (...) order. Accordingly, initial arterial endothelial cell differentiation occurs outside of arterial vessels. These pre‐artery cells then build trees by following a migratory path from smaller into larger arteries, a process guided by the forces imparted by blood flow. Thus, in comparison to other branched organs, arteries can obtain their structure through inward growth and coalescence. Here, new information on the underlying mechanisms is discussed, and how defects can lead to pathologies, such as hypoplastic arteries and arteriovenous malformations. -/- . (shrink)

In the late 1990s, when otherwise healthy women in Aotearoa New Zealand started to die as a result of venous thrombosis attributed to third generation oral contraceptive pills, this contraceptive technology became the subject of media scrutiny and professional re-investigation. This research utilizes a qualitative methodology to explore the accounts of a small selection of contraceptive consumers. Many of this study’s consumers constructed an alternative framing of the 3GOC controversy, which accessed official information (such as medical statistics) but critically (...) framed these facts by grounding them in relation to how their bodies reacted to pharmaceuticals. Bricolage is used as a metaphor for thinking about the ways that women engage in decision-making by creating ‘toolboxes’ from a multitude of readily available material and information. Lévi-Strauss’s original formulation of bricolage, in particular the claim that bricoleurs do not create ‘new knowledge’, is critiqued. (shrink)

There are three main categories of rationale for withholding information or telling lies: if overwhelming harm can only be averted through deceit; complete triviality such that it is irrelevant whether the truth is told; a duty to protect the interests of others. Public health authorities are frequently having to form judgements about the public interest, whether to release information or issue warnings. In June 1992, routine surveillance detected patulin levels (a known carcinogen) in samples of apple juice exceeding safety threshold. (...) Remedial actions were promptly taken and it was planned to subsequently publish the information in the routine way. However, the media portrayed the handling of the problem as a conspiracy and there was a short term reduction in juice sales. In October 1995, the UK Committee on Safety of Medicines issued a warning about certain brands of the contraceptive pill, based on the interim results of three unpublished studies. The increased risk of thromboembolism was small, but the resulting scare led to an increase in unwanted pregnancies. The handling of the B.S.E. crisis in the U.K. also led to accusations of incompetence or conspiracy. Public health authorities have to handle uncertainty and frequently have to form judgements for public safety on the basis of evidence of poor quantity and quality. Their task is not helped by the sometimes conflicting agenda of scientists and media. The public also have differing perceptions and interpretations of risk. The series of scares and crises are having a detrimental effect on public confidence in public health authorities. (shrink)

Gliomas can display marked changes in the concentrations of energy metabolism molecules such as creatine (Cr), phosphocreatine (PCr) and lactate, as measured using magnetic resonance spectroscopy (MRS). Moreover, the BOLD (blood oxygen level dependent) contrast enhancement in functional magnetic resonance imaging (fMRI) can be reduced or missing within or near gliomas, while neural activity is not significantly reduced (so-called neurovascular decoupling), so that the location of functionally eloquent areas using fMRI can be erroneous. In this paper, we adapt a previously (...) developed model of the coupling between neural activation, energy metabolism and hemodynamics, by including the venous dilatation Balloon model of Buxton and Frank. We show that decreasing the cerebral blood flow (CBF) baseline value, or the CBF increase fraction, results in a decrease of the BOLD signal and an increase of the lactate peak during a sustained activation. Baseline lactate and PCr levels are not significantly affected by CBF baseline reduction, but are altered even by a moderate decrease of mitochondrial respiration. Decreasing the total Cr and PCr concentration reduces the BOLD signal after the initial overshoot. In conclusion, we suggest that the coupled use of BOLD fMRI and MRS could contribute to a better understanding of the neurovascular and metabolic decoupling in gliomas. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Confidentiality and Its LimitsMaude Laliberté, John D. Lantos, and Sonia GowdaMultiple sclerosis is believed to be an autoimmune disease of the central nervous system. However, according to Italian physician Paolo Zamboni, it is related to cerebrospinal vascular insufficiency. Zamboni claims that MS can be treated by remedying this condition with venous angioplasty. This surgery is offered as treatment for MS in various countries—Poland, Bulgaria, and Costa Rica, for (...) example. But the Medical Board of Quebec, Canada, does not allow its members to perform the surgery and strongly advises patients against seeking it elsewhere. This opposition is based on the lack of evidence to support the procedure and the serious risks associated with it (including venous thrombosis, stroke, and pulmonary embolism). As a result, many Canadian MS patients have traveled to other countries to receive the surgery. Quebec physicians have been reluctant to provide surgical follow-up for patients who undergo the surgery in other countries due to the lack of information regarding the procedure. No alternative treatments are effective to partially or completely cure MS, and so the treatments available in Canada aim only to manage its symptoms.Jade is a forty-year-old Canadian woman with MS. She is on long-term disability leave, complains of growing fatigue and muscle stiffness, and has painful sensations in her limbs. She has been followed by an interdisciplinary team in a specialized hospital in Quebec for the past twenty years, since she was diagnosed. At her last appointment, Jade told her physical therapist that she recently underwent the experimental Zamboni surgery in Poland, despite her physician’s strong recommendation not to. Jade fears her physician’s reaction, so she asks the physical therapist to keep this information from the rest of her medical team.Jade is shy and tends to distrust health care professionals. It took many years for her physical therapist to gain her trust and to develop a positive therapeutic relationship with her. However, the physical therapist knows that serious complications can occur in patients who have had Zamboni’s surgery. Not telling Jade’s physician about the surgery could result in harm; Jade could have complications that are not recognized. Providing the information to the rest of the team would allow them to adjust her treatment to respond to the surgery and give her information and postoperative education that she will need. Moreover, keeping this secret could threaten team cohesion and trust if they find out about it later.Jade decided to undergo a risky surgery against her doctor’s advice in the hope of improving her quality of life. This was her autonomous choice. How should the physical therapist respond?CommentaryMaude Laliberte (bio)Laws and professional codes of ethics direct clinicians to respect their patients’ autonomy through confidentiality and informed consent unless there are compelling reasons not to do so. Health professionals are deeply committed to helping patients; above all, they want to avoid harming them. Therefore, a key component of this case is the possibility that respecting Jade’s desire to conceal information from the team may put her at direct risk if any postoperative complications are not detected, and at indirect risk if Jade’s trust in her medical team is undermined to the point where she turns away from them.The physical therapist must determine if the possible physical risks to Jade are imminent and serious enough to go against her autonomous choice. One risk that can occur following Zamboni’s surgery is inflammation of a vein caused by a blood clot. This is a life-threatening situation (although it may not be a likely complication for Jade). But the physical therapist can teach Jade to recognize the physical signs that can alert her to this problem, giving her ample time to seek treatment. Thus, even though she may be in danger from a life-threatening risk, there may be ways to manage it besides violating her confidentiality.The respect for autonomous choice is a crucial aspect of our democratic values. It promotes a process of exchange in the therapeutic alliance: the professional guides and informs the patient, but the patient is a partner in care planning and treatment. An important... (shrink)

William Harvey's famous quantitative argument fromDe motu cordis about the circulation of blood explained how a small amount of blood could recirculate and nourish the entire body, upending the Galenic conception of the blood's motion. This paper argues that the quantitative argument drew on the calculative and rhetorical skills of merchants, including Harvey's own brothers. Modern translations ofDe motu cordisobscure the language of accountancy that Harvey himself used. Like a merchant accounting for credits and debits, intake and output, goods and (...) moneys, Harvey treated venous and arterial blood as essentially commensurate, quantifiable and fungible. For Harvey, the circulation of blood was an arithmetical necessity. The development of Harvey's circulatory model followed shifts in the epistemic value of mercantile forms of knowledge, including accounting and arithmetic, also drawing on an Aristotelian language of reciprocity and balance that Harvey shared with mercantile advisers to the royal court. This paper places Harvey's calculations in a previously underappreciated context of economic crisis, whose debates focused largely on questions of circulation. (shrink)

Ojectives Low energy hip fractures are one of the greatest causes of morbidity and mortality in orthopaedics. This study aims to evaluate written consent forms with respect to basic standards as set out in the Good Practice in Consent Initiative. In particular the stated risks and benefits of each procedure were assessed. Methods 100 consecutive consent forms were reviewed prospectively. The stated procedure, side and complications were recorded. Appropriate signature and legibility was assessed. 13 consultant orthopaedic surgeons were surveyed to (...) identify what risks and benefits they thought should be stated. Results Of 100 consent forms, 31 were for patients who are unable to consent. All 100 consent forms were correctly filled in with patient details and signed. 98% were legible. All stated the side of the operation. The number of complications listed per form ranged from 4 to 11. Infection, bleeding and thromboembolic complications were stated in the majority of consent forms. In total, 30 different complications were recorded; some were only stated once. Discussion and Conclusions This work suggests consent forms are completed well with respect to patient identifiers, legibility and procedure. The variability of complications stated is vast. We suggest standard pre-printed consent forms containing risks and benefits should be used as this may improve standards of informed consent. This has also been recently supported by the British Orthopaedic Association. (shrink)

Authors De Marco and colleagues have presented a new model on the concept of invasiveness, redefining both its technical definition and practical implementation.1 While the authors raise valid critiques regarding the discrepancy in definitions, I cannot help but wonder about the purpose of redefining terms for which little confusion, if any, exists? This commentary seeks to scrutinise the rationale supporting the new model in the absence of significant clinical confusion and to explore the implications for clinical practice. Initially, one may (...) notice there is no mention of clinical relevancy, confusion among patients or whether the discrepancy in terms is causing miscommunication. It seems reasonable that some clinical confusion may exist, but so too does a similar imbalance of terms when speaking technically across the specialties; take depression and its definition as a primary example. While I certainly agree with the illustration of non-invasive prenatal testing being compared with venous blood draws as a disparity in terminology, little evidence suggests confusion concerning the nosology.2 The medical community, including both physicians and patients, recognises that the terminology is specifically used within the …. (shrink)

It is well known that Harvey was influenced by Aristotle. This paper seeks to show that Harvey's quantitative argument for the circulation and his analogy of the heart with a pump do not go beyond Aristotle and may even have been inspired by passages in Aristotle. It also considers the fact that Harvey gives much greater prominence to a macrocosm/microcosm analogy between the weather cycle and the circulation of the blood than he does to the pump analogy. This analogy is (...) prominent in both the preface to the king and pivotal chapter eight of De Motu Cordis, and may indicate a significant influence from the Renaissance natural magic tradition. The full implications of this analogy are critical for Harvey's conception of the nature of the circulation, especially the constant interconversion of venous and arterial blood and the passage of blood through the lungs. The tendency to assume that Harvey had a superior method since he made such an important discovery may have led not only to overestimation of the influence from the new science of the seventeenth century, but also to underestimation of influence from the magical tradition. (shrink)

The establishment of a functional vascular system requires multiple complex steps throughout embryogenesis, from endothelial cell (EC) specification to vascular patterning into venous and arterial hierarchies. Following the initial assembly of ECs into a network of cord‐like structures, vascular expansion and remodeling occur rapidly through morphogenetic events including vessel sprouting, fusion, and pruning. In addition, vascular morphogenesis encompasses the process of lumen formation, critical for the transformation of cords into perfusable vascular tubes. Studies in mouse, zebrafish, frog, and human (...) endothelial cells have begun to outline the cellular and molecular requirements underlying lumen formation. Although the lumen can be generated through diverse mechanisms, the coordinated participation of multiple conserved molecules including transcription factors, small GTPases, and adhesion and polarity proteins remains a fundamental principle, leading us closer to a more thorough understanding of this complex event. (shrink)

Transcranial magnetic stimulation studies have demonstrated increased cortical facilitation and reduced inhibition following aerobic exercise, even when examining motor regions separate to the exercised muscle group. These changes in brain physiology following exercise may create favorable conditions for adaptive plasticity and motor learning. One candidate mechanism behind these benefits is the increase in brain-derived neurotropic factor observed following exercise, which can be quantified from a venous blood draw. The aim of this study was to investigate changes in motor cortex (...) excitability and inhibition of the upper limb, and circulating BDNF, following high-intensity interval training on a stationary bicycle. Nineteen sedentary adults participated in a randomized crossover design study involving a single bout of high-intensity interval cycling for 20 min or seated rest. Venous blood samples were collected, and transcranial magnetic stimulation was used to stimulate the extensor carpi radialis, where motor evoked potentials were recorded pre- and post-condition. Following exercise, there was a significant increase in corticospinal excitability measured at 120% of resting motor threshold and a reduction in short-interval cortical inhibition. There was a non-significant 23.6% increase in BDNF levels. Collectively, these results reflect a net reduction in gamma aminobutyric acid ergic synaptic transmission and increased glutamatergic facilitation, resulting in increased corticospinal excitability. This study supports the notion that acute high-intensity exercise provides a potent stimulus for inducing cortical neuroplasticity, which may support enhanced motor learning. (shrink)

SummaryIn 1968, a prospective study was started in collaboration with the Family Planning Association to try to provide a balanced view of the beneficial and harmful effects of different methods of contraception. This investigation is now in progress at seventeen clinics and over 17,000 women are under observation. At the time of recruitment, all these women were married white British subjects, aged 25–39 years, who voluntarily agreed to participate. Fifty-six per cent were using oral contraceptives, 25% were using a diaphragm (...) and 19% were using an intrauterine device. During follow-up each woman is questioned at return visits to the clinic and a record of pregnancies and their outcome, hospital referrals, changes in contraceptive methods and the results of cervical smears, is accumulated. Women who default are sent a postal questionnaire and, if this is not returned, are telephoned or visited in their homes to collect the necessary information.So far, data obtained during 56,000 woman-years of observation are available for analysis. Follow-up has been maintained with an annual lapse rate of about 0.3%due to withdrawal of co-operation or loss of contact; adherence to the method of contraception in use at recruitment has been reasonably good, and the reporting of pregnancies and hospital admissions appears to have been both reliable and unbiased.The present data include only 24 deaths, so the mortality associated with different contraceptive methods cannot yet be estimated. With regard to morbidity, however, our preliminary results closely resemble those obtained in the prospective study carried out by the Royal College of General Practitioners and in the principal retrospective studies carried out in Britain and the United States. Women who used oral contraceptives at the start of the study experienced adeficiencyof hospital referrals for cancer, benign lesions of the breast, menstrual disorders other than amenorrhoea, duodenal ulcer, and retention cysts of the ovary; they showed anexcessof referrals for cerebrovascular disease, cervical erosion, skin disorders, self-poisoning, migraine, venous thrombosis and embolism, hayfever, gallbladder disease, amenorrhoea, and sterility. Women who used a diaphragm showed adeficiencyof hospital referrals for carcinoma-in-situ and dysplastic lesions of the cervix uteri and accidental injury; and anexcessof referrals for haemorrhoids and cystitis. Women who used an IUD experienced anexcessof hospital referrals for anaemia, varicose veins and salpingitis. About half of these differences were predicted from other studies while some suggestive evidence already existed for a further five. Of the remaining six, some probably reflect the influence of selective factors or chance.Multiple pregnancies, stillbirths, malformations, the sex ratio and birthweight showed no consistent relationship to method of contraception. The outcome of unplanned pregnancies occurring in women using an IUD, however, was remarkably unfavourable both in terms of ectopic gestation and miscarriage.Clear evidence was found of impairment of fertility after discontinuation of oral contraceptives. Whether this is likely to lead to permanent sterility in some women is uncertain.The study has provided data on the efficacy of a wide variety of contraceptive methods. In general the failure rates are in keeping with those obtained in other large-scale studies, save that those for the diaphragm and the sheath are much lower than those usually quoted.The available evidence does not yet allow a final balance to be struck between the benefits and risks associated with the new methods of contraception that have become widely used during the last two decades. It seems clear, however, that there are no material risks associated with the use of the diaphragm apart from the risk of pregnancy and that there may be some unintended benefits. (shrink)

Vascular development entails multiple cell‐fate decisions to specify a diverse array of vascular structures. Notch proteins are signaling receptors that regulate cell‐fate determination in a variety of cell types. The finding that Notch genes are robustly expressed in the vasculature suggests roles for Notch in guiding endothelial and associated mural cells through the myriad of cell‐fate decisions needed to form the vasculature. In fact, mice with defects in genes encoding Notch, Notch ligands, and components of the Notch signaling cascade invariably (...) display vascular defects. Human Notch genes are linked to Alagille's Syndrome, a developmental disorder with vascular defects, and CADASIL, a cerebral arteriopathy. Studies in zebrafish, mice and humans indicate that Notch works in conjunction with other angiogenic pathways to pattern and stabilize the vasculature. Here, we will focus on established functions for Notch in vascular remodeling and arterial/venous specification and more speculative roles in vascular homeostasis and organ‐specific angiogenesis. BioEssays 26:225–234, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The human blood coagulation system comprises a series of linked glycoproteins that upon activation induce the generation of downstream enzymes ultimately forming fibrin. This process is primarily important to arrest bleeding (hemostasis). Hemostasis is a typical example of a molecular machine, where the assembly of substrates, enzymes, protein cofactors and calcium ions on a phospholipid surface markedly accelerates the rate of coagulation. Excess, pathological, coagulation activity occurs in “thrombosis”, the formation of an intravascular clot, which in the most dramatic form (...) precipitates in the microvasculature as disseminated intravascular coagulation. Thrombosis occurs according to a biochemical machine model in the case of atherothrombosis on a ruptured atherosclerotic plaque, but may develop at a slower rate in venous thrombosis, illustrating that the coagulation machinery can act at different velocities. The separate coagulation enzymes are also important in other biological processes, including inflammation for which the rapid conversion of one coagulation factor by the other is not a prerequisite. The latter role of coagulation enzymes may be related to the old and probably maintained function of the coagulation machine in innate immunity. BioEssays 25:1220–1228, 2003. © 2003 Wiley Perioicals, Inc. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:“Just Because You Can—Doesn’t Mean You Should”Mindy B. StatterAs Albert R. Jonsen stated, “The technological imperative begins to rule clinical decisions: if a technology exists, it must be applied. Patients... are moved to higher and higher levels of care, finally becoming enmeshed in a tangle of tubes that extinguish their identity and needs as persons.” In this case the conflict created by the parental demand for the utilization of (...) technology, extracorporeal support in a neonate will be explored.I was consulted in the care of a newborn with a right–sided congenital diaphragmatic hernia (CDH). In this anomaly the diaphragm, the muscular partition that separates the abdomen and the thorax, forms incompletely, and the viscera migrate up into the chest compressing the developing lung, shifting the medistinum and heart and compressing the contralateral lung. The resulting lung maldevelopment is termed pulmonary hypoplasia. The maldevelopment of the lungs in CDH is variable with the most severe forms resulting in neonatal death. This congenital anomaly is associated with 55% survivability; the poor prognosis is due to the pulmonary hypoplasia. In addition to pulmonary hypoplasia, there is the association of pulmonary hypertension with CDH. Pulmonary hypertension is a condition where the vascular resistance in the lung is high with reduced blood flow within the lung. The physiologic consequence of pulmonary hypertension is hypoxemia, oxygen deficiency in the blood, and reduced oxygen delivery to all organs. Unlike severe pulmonary hypoplasia, pulmonary hypertension is reversible. When an infant with CDH is born and deteriorates due to respiratory failure it can be difficult to determine whether the respiratory failiure is due to pulmonary hypoplasia or pulmonary hypertension. Extracorporeal membrane oxygenation (ECMO) is indicated in the management of reversible respiratory and, or cardiac failure. In the case of neonates with CDH, ECMO addressess the reversible component of the respiratory failure, the pulmonary hypertension. The respiratory failure due to severe pulmonary hypoplasia is not reversible; ECMO is not indicated. There are established criteria to guide the determination of which infant is a candidate for ECMO. Depending upon the ECMO center, the stringency can vary.In this case, the baby had significant respiratory failure with impairment in both oxygenation, hypoxia, and ventilation–the elimination of carbon dioxide, hypercapnea. The neonatologist spoke with the mother who stated that she wanted “everything done” including ECMO in the management [End Page 22] of her baby. When the neonatologist consulted me to put the baby on ECMO I expressed my concern that this infant had irreversible respiratory failure due to pulmonary hypoplasia. And simply from a technical aspect, I could not guarantee that ECMO would “work”. When an infant is “cannulated” for extracorporeal support, cannulas are inserted to allow for the drainage of blood into the ECMO circuit, the blood oxygenated and the carbon dioxide is cleared, and the blood is then returned to the infant. The majority of diaphragmatic hernias are on the left and when the CDH is on the right side, the right heart may be compressed by the viscera in the chest, and venous drainage into the ECMO circuit may be impaired. When this is encountered, the next step in the management algorithm is to fix the hernia–reduce and return the viscera within the chest to the abdomen and eliminate the visceral compression of the right heart. The neonatologist shared my concern and also reiterated that this baby’s mother wanted “everything done”. I had little uncertainty as to the etiology of the respiratory failure in this baby. In meeting the mother’s demands I then suggested that the hernia be repaired first, and if there was improvement in the hypoxia and hypercapnea, then give the baby the benefit of the doubt that there is a component of reversibility to the respiratory failure and then proceed with ECMO cannulation. The neonatologist agreed with this suggested plan.I then went to talk with the baby’s mother. I explained my concerns that based on the profound hypercapnea on the arterial blood gases that the baby’s respiratory failure was due to pulmonary hypoplasia and not reversible with extracorporeal support. She insisted that her baby be put on ECMO. I then explained the operative algorithm and... (shrink)

Pain is the single most common reason patients seek care in the emergency department. Given the prevalence of pain as a presenting complaint, one might expect emergency physicians to assign its treatment a high priority; however, pain is often seemingly invisible to the emergency physician. Multiple research studies have documented that the undertreatment of pain, or oligoanalgesia, is a frequent occurrence. Pain that is not acknowledged and managed appropriately causes dissatisfaction with medical care, hostility toward the physician, unscheduled returns to (...) the emergency department, delayed return to full function, and potentially, an increased risk of litigation. Failure to recognize and treat pain may result in anxiety, depression, sleep disturbances, increased oxygen demands with the potential for end organ ischemia, and decreased movement with an increased risk of venous thrombosis. (shrink)

Pain is the single most common reason patients seek care in the emergency department. Given the prevalence of pain as a presenting complaint, one might expect emergency physicians to assign its treatment a high priority; however, pain is often seemingly invisible to the emergency physician. Multiple research studies have documented that the undertreatment of pain, or oligoanalgesia, is a frequent occurrence. Pain that is not acknowledged and managed appropriately causes dissatisfaction with medical care, hostility toward the physician, unscheduled returns to (...) the emergency department, delayed return to full function, and potentially, an increased risk of litigation. Failure to recognize and treat pain may result in anxiety, depression, sleep disturbances, increased oxygen demands with the potential for end organ ischemia, and decreased movement with an increased risk of venous thrombosis. (shrink)

BackgroundIn 2009, Dr. Paolo Zamboni proposed chronic cerebrospinal venous insufficiency (CCSVI) as a possible cause of multiple sclerosis (MS). Although his theory and the associated treatment (“liberation therapy”) received little more than passing interest in the international scientific and medical communities, his ideas became the source of tremendous public and political tension in Canada. The story moved rapidly from mainstream media to social networking sites. CCSVI and liberation therapy swiftly garnered support among patients and triggered remarkable and relentless advocacy (...) efforts. Policy makers have responded in a variety of ways to the public’s call for action.DiscussionWe present three different perspectives on this evolving story, that of a health journalist who played a key role in the media coverage of this issue, that of a health law and policy scholar who has closely observed the unfolding public policy developments across the country, and that of a medical ethicist who sits on an expert panel convened by the MS Society of Canada and the Canadian Institutes of Health Research to assess the evidence as it emerges.SummaryThis story raises important questions about resource allocation and priority setting in scientific research and science policy. The growing power of social media represents a new level of citizen engagement and advocacy, and emphasizes the importance of open debate about the basis on which such policy choices are made. It also highlights the different ways evidence may be understood, valued and utilized by various stakeholders and further emphasizes calls to improve science communication so as to support balanced and informed decision-making. (shrink)