A comparison of angina symptoms reported by clinicians and patients, pre and post revascularisation: Insights from the Stent or Surgery Trial.

BACKGROUND: There are limited data comparing the consistency of angina reporting by patients and clinicians. METHODS: We performed a retrospective analysis of data from the randomised Stent or Surgery (SoS) trial. The trial required reporting of angina using the Canadian Cardiovascular Society (CCS) classification by both patients and clinicians at baseline and twelve months. We compared paired observations to describe the magnitude and direction of differences in clinician and patient reporting. The difference in CCS grade was expressed as the clinician minus patient value. We also examined the proportion of trial subjects reported as being free from angina (CCS = 0) in clinician and patient reporting. RESULTS: Paired CCS data was available for 912 and 887 cases at baseline and 12 months respectively. At baseline, clinicians reported freedom from angina in a single case (1/912 = 0.1%) compared to 70/912 (7.7%) patients (Delta 7.6% 95% CI 5.8 to 9.3, P ≤0.001). At 12 months, the position was reversed, with clinicians reporting 639/887 (72%) angina free compared to 449/887 (50.6%) for patients (Delta -21.4 95% CI -17.1 to -25.8 P ≤ 0.001). For the reported CCS grade at follow-up, the weighted linear kappa for overall agreement was 0.312. Discordant reporting involved the clinician suggesting less angina rather than more (36% v 8% of cases). CONCLUSIONS: These findings have implications for our perception of previous research which has, in the main, focussed on clinician reporting. This emphasises the importance of patient reporting and a need to better understand reasons for discordance.

Gene therapy for restenosis--what now, what next?

Late luminal loss after coronary angioplasty has resisted pharmacological and physical attempts at prevention for over twenty years. As a consequence of the resistance of restenosis to traditional therapeutic approaches it has become a popular target for DNA-based treatment modalities. In this review we consider what is currently known of the basic pathophysiology of restenosis and briefly outline the previous attempts to influence the long-term outcome after coronary intervention. We then discuss the animal models of vascular injury that have been used for studies of gene therapy and the vectors that have been applied to the setting of vascular gene transfer before considering the many studies in which the effects of specific gene transfer have been studied in the setting of vascular injury. These transgenes are considered in four broad groupings: those that act by the suppression of cellular proliferation in the vessel wall; those that inhibit cell migration; anti-thrombotic transgenes; and transgenes that have multiple effects within the vessel. We finally consider why, although more than eight years have passed since publication of the first studies of gene transfer to inhibit the vascular responses to endoluminal injury, little progress has been made in translating gene therapy for restenosis into the human setting. Principle reasons for the disappointingly slow clinical implementation of gene therapy for restenosis are an incomplete understanding of the vascular biology of restenosis, the difficulty of translating findings in animal models into the human setting and the technical difficulties incumbent upon localised gene delivery into coronary arteries.

A novel combination of promoter and enhancers increases transgene expression in vascular smooth muscle cells in vitro and coronary arteries in vivo after adenovirus-mediated gene transfer.

Recombinant adenoviruses are employed widely for vascular gene transfer. Vascular smooth muscle cells (SMCs) are a relatively poor target for transgene expression after adenovirus-mediated gene delivery, however, even when expression is regulated by powerful, constitutive viral promoters. The major immediate-early murine cytomegalovirus enhancer/promoter (MIEmCMV) elicits substantially greater transgene expression than the human cytomegalovirus promoter (MIEhCMV) in all cell types in which they have been compared. The Woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) increases transgene expression in numerous cell lines, and fragments of the smooth muscle myosin heavy chain (SMMHC) promoter increase expression within SMC from heterologous promoters. We therefore, compared the expression of beta-galactosidase after adenovirus-mediated gene transfer of lacZ under the transcriptional regulation of a variety of combinations of the promoters and enhancers described, in vitro and in porcine coronary arteries. We demonstrate that inclusion of WPRE and a fragment of the rabbit SMMHC promoter along with MIEmCMV increases beta-galactosidase expression 90-fold in SMC in vitro and approximately 40-fold in coronary arteries, compared with vectors in which expression is regulated by MIEhCMV alone. Expression cassette modification represents a simple method of improving adenovirus-mediated vascular gene transfer efficiency and has important implications for the development of efficient cardiovascular gene therapy strategies.

Hypertension in end-stage renal disease.

Chronic renal failure is common. Recent estimates from the United States suggest that one in 10 adults has an elevated serum creatinine. Hypertension and renal disease are intimately connected at many levels, and clearly accelerate each other s course. Hypertension is an almost universal feature of end-stage renal disease, a state of frightening cardiovascular risk. Surprisingly, most recent observational studies have shown an association between low blood pressure and increased mortality, a result that may engender therapeutic nihilism in the absence of large randomised trials. This observation may be due to reverse causality, as the age and cardiovascular comorbidity of patients reaching end-stage renal disease is considerable. When outcomes other than death are considered, especially progressive left ventricular hypertrophy, but also ischaemic heart disease and congestive heart failure, more predictable and expected associations are seen, with rising blood pressure appearing to be a deleterious parameter. Uraemia appears to be a state of premature senescence, and arterial rigidity, whose clinical corollary is wide pulse pressure, is a characteristic feature. Recent observational studies have focused on pulse pressure, rather than the traditional approach of analysing its components, systolic and diastolic blood pressure, in isolation. High pulse pressure appears to be a marker of short survival in dialysis patients, but disentangling this association from old age and pre-existing cardiovascular conditions is challenging. Remarkably, and regrettably, no large scale randomised controlled studies examining strategies that tackle the issue of hypertension in dialysis patients have yet to be initiated.

Magnetic resonance imaging of pulmonary damage in the term and premature rat neonate exposed to hyperoxia.

Immaturity and oxygen toxicity have been implicated in the pathogenesis of the neonatal disease bronchopulmonary dysplasia. The present study aimed to investigate the use of magnetic resonance imaging (MRI) to assess hyperoxia-mediated lung injury in the term and premature neonate. Term (gestation, 22 d) and premature (21 d) rat pups were exposed to hyperoxia (>95%) or air for a 6-d period (n = 7) and assessed for lung damage by MRI. Pulmonary signal intensities of T1-weighted images were significantly increased in both hyperoxia-exposed term and premature neonates, relative to air-breathing controls (p < 0.01). T2-weighted MRI signal intensities were also greater in premature and term rat pups exposed to hyperoxia, but failed to reach significance (p > 0.05). Elevated MRI pulmonary signal intensities may have represented an increase in magnetic resonance-detectable free water, possibly indicating an increase in edema. Corresponding histologic evidence of lung injury was detected in both term and premature rat pups exposed to hyperoxia. Histologic samples indicated focal regions of alveolar hemorrhage, immune cell infiltration, edema, and collapse in both term and premature rat neonates exposed to hyperoxia. Alveolar air space was assessed (n = 5) by light microscopy within a 0.5 mm2 region of the superior left and inferior right pulmonary lobes of each treatment group. Alveolar area of the superior left lung lobe of the premature hyperoxia treatment group was significantly smaller than other treatment groups (p < 0.05). Reduced area for respiratory exchange was probably a result of observed focal areas of edema and collapse. MRI-detectable increases in lung signal intensity may have represented an increase in hyperoxia-induced pulmonary edema in the 6-d-old rat neonate. Increases in signal intensity correlated with the appearance of edema in pulmonary histologic samples. Premature delivery had a less defined effect on lung injury but possibly exacerbated hyperoxia-mediated pulmonary damage.

E-health & pharmaceuticals.

Drug firms are integrating technology into the continuum of care. They're enlisting physicians to use their technology in prescribing medications, reporting clinical data, and learning about new drugs. They're also building a loyal customer base, and they're doing it smartly.

Health care.com. Trustees may soon find themselves on the board of an Internet startup.

The Internet is no longer a technology gimmick or a luxury for providers. It is already changing marketing strategies and may some day fundamentally alter the way health care is delivered.

Media management of a community outbreak of meningococcal meningitis.

Cases and, particularly, clusters of meningococcal meningitis often create high levels of public concern and attract the interest of news media. We describe below our experience of managing intense local and national media interest during a community outbreak of meningococcal disease in Derbyshire. Our learning is set out as ten key recommendations. Four of these are around managing the media, including using a proactive press release, providing detailed briefings, using a single spokesperson and coordination of the response by a press officer experienced in media management. Another four describe how to deliver an appropriate on-site response, often requested during community intervention programmes. The two final recommendations relate to ensuring good communication and supporting staff during what is an intensely stressful period. We hope our experiences may help others if faced with a similar problem.

Net gain or net loss? Health care consumers become Internet savvy.

The Internet is overloaded with health care information, and consumers can't seem to get enough of it. As a result, patients are now more knowledgeable about their treatment options when they meet with doctors. That's the good news; the bad news is that the doctors themselves must sort through all the sometimes contradictory, sometimes inaccurate information.

Host-dependent and seasonal variation in opisthaptoral hard parts of Gyrodactylus cf. arcuatus from three Pomatoschistus spp. and G. arcuatus from Gasterosteus aculeatus: a multivariate approach.

Gyrodactylus arcuatus-like monogeneans collected from the gills of 3 goby species, Pomatoschistus minutus, P. lozanoi and P. pictus, from the Voordelta Area (SW Netherlands) were compared on a morphometric basis with G. arcuatus from its type host, the three-spined stickleback, Gasterosteus aculeatus. Univariate and multivariate analysis was carried out on measurements of 17 characters of the opisthaptoral hard parts of 268 specimens. The contribution of host-dependent and seasonal factors to the observed morphological variation are discussed. Univariate statistics (ANOVA) were used to detect features that were useful in separating the gyrodactylids from the different host groups. Subsequent factor analysis and discriminant analysis, combining all variables, led to the separation of 3 distinct forms (possibly species) dependent on the host species harbouring them. G. arcuatus (sensu stricto) was only present on G. aculeatus, while P. minutus and P. lozanoi carried a common species, Gyrodactylus sp. 1, and P. pictus hosted Gyrodactylus sp. 2. Seasonal variation in size of the sclerities was demonstrated on the Gyrodactylus species from P. minutus and P. lozanoi, and should be taken into consideration when specimens are compared. The findings are discussed in view of the possibility of phylogenetic host specificity of the gyrodactylids occurring on goby species that live sympatrically in the Voordelta area.

10 CEO resources.

With computer woes marching into the front office and onto the front page these days, it's time to bone up. This guide to books, Web sites, and other executive resources will get you started.

Web-o-matic isn't automatic--yet. Internet technology hasn't broken the barrier between doctors & computers.

Internet technologies sound like all the right moves for bringing doctors into the computer loop. They're cheap, fast, and offer a simple way to tap information, creating a virtual electronic medical record. But doctors are leaving their laptops idle and asking office staff to print out paper records.

The effect of Gyrodactylus salaris (Monogenea) on the epidermis of Atlantic salmon, Salmo salar, parr in the river Batnfjordselva, Norway.

Skin morphology of Atlantic salmon, Salmo salar, parr infected with Gyrodactylus salaris was examined for 3 yr in the river Batnfjordselva in Norway and compared to that of uninfected salmon parr from a neighboring river. The epidermis of the infected population had more cell layers and was thicker than the epidermis of parr from the uninfected population. The number of mucous cells did not differ, and no seasonal changes in morphology of the epidermis were detected in either rivers. Intensity of G. salaris did not correlate to epidermal thickness, epidermal cell layers, or mucous cell concentration.