Invited review: Carryover effects of early lactation feeding on total lactation performance in dairy cows.

In comparison with the intensive research on the direct effects of energy supply on dairy cow lactation performance, little attention has been paid to the effect of early lactation feeding on subsequent production. The present paper reviews 9 studies carried out with the aim of quantifying the immediate and subsequent responses in milk production and body weight to early lactation feeding. Most results showed that a more generous feeding in early lactation caused a positive carryover effect on subsequent production, whereas an inadequate level of feed in early lactation has been shown to reduce subsequent milk yield. The carryover periods ranged from 3 to 12 wk and the difference in milk yield between cows in the carryover periods ranged between 1.5 and 4.5kg of milk/cow per day. When calculated as a percentage of the immediate effect, the carryover effect ranged from 22 to 63%. In 2 of the 9 papers reviewed, the authors found no carryover effect, probably due to the long post-treatment periods in these studies. This is supported by the other studies in which the carryover effect was only significant in a limited period after end of treatment. The magnitude of the carryover effect seems to be determined by several factors including duration of the treatment and post-treatment feeding level. The most important factor though appears to be the magnitude of over- or underfeeding (i.e., a strong relationship between the treatment period feeding level and the subsequent response in production).

Glyburide increases risk in patients with diabetes mellitus after emergent percutaneous intervention for myocardial infarction--a nationwide study.

BACKGROUND: Sulfonylureas have been linked to an increased cardiovascular risk by inhibition of myocardial preconditioning. Whether individual sulfonylureas affect outcomes in diabetic patients after emergent percutaneous coronary intervention for myocardial infarction is unknown. METHODS: All Danish patients receiving glucose-lowering drugs admitted with myocardial infarction between 1997 and 2006 who underwent emergent percutaneous coronary intervention were identified from national registers. Multivariable Cox proportional hazards models were used to analyze the risk of cardiovascular mortality and morbidity associated with sulfonylureas. RESULTS: A total of 926 patients were included and 163 (17.6%) patients died during the first year of which 155 (16.7%) were cardiovascular deaths. The most common treatment was sulfonylureas which were received by 271 (29.3%) patients, and 129 (13.9%) received metformin. Cox proportional hazard regression analyses adjusted for age, sex, calendar year, comorbidity and concomitant pharmacotherapy showed an increased risk of cardiovascular mortality (hazard ratio [HR] 2.91, 95% confidence interval [CI] 1.26-6.72 ; p=0.012), cardiovascular mortality and nonfatal myocardial infarction (HR 2.69 , 95% CI 1.21-6.00; p=0.016), and all-cause mortality (HR 2.46, 95% CI 1.11-5.47; p=0.027), respectively, with glyburide compared to metformin. CONCLUSIONS: Glyburide is associated with increased cardiovascular mortality and morbidity in patients with diabetes mellitus undergoing emergent percutaneous coronary intervention after myocardial infarction. Early reperfusion therapy is the mainstay in modern treatment of myocardial infarction and the time may have come to discard glyburide in favour of sulfonylureas that do not appear to confer increased cardiovascular risk.

Psoriasis is associated with clinically significant cardiovascular risk: a Danish nationwide cohort study.

OBJECTIVE: The magnitude of the cardiovascular risk from psoriasis and psoriatic arthritis is debated. We therefore investigated the psoriasis-related risk of adverse cardiovascular events and mortality. DESIGN, SETTING AND SUBJECTS: We conducted a cohort study of the entire Danish population aged ≥18 years followed from 1997 to 2006 by individual-level linkage of nationwide registers. Psoriasis was defined by prescription claims and classified as severe if patients received hospital-based treatment. Time-dependent Poisson regression models were applied to assess cardiovascular risk in patients with psoriasis and psoriatic arthritis. MAIN OUTCOME MEASURES: All-cause mortality, cardiovascular mortality and hospitalizations for myocardial infarction (MI), stroke and coronary revascularization were recorded. RESULTS: A total of 34 371 patients with mild psoriasis and 2621 with severe psoriasis, including 607 with psoriatic arthritis, were identified and compared with 4 003 265 controls. The event rates and rate ratios (RRs) of all-cause mortality, cardiovascular death, MI, coronary revascularization, stroke and a composite of MI, stroke and cardiovascular death were increased in patients with psoriasis. The rate ratio increased with disease severity and decreased with age of onset. The overall RRs for the composite endpoint were 1.20 (95% confidence interval [CI] 1.14-1.25) and 1.58 (95% CI 1.36-1.82) for mild and severe psoriasis, respectively. The corresponding RRs for cardiovascular death were 1.14 (95% CI 1.06-1.22) and 1.57 (95% CI1.27-1.94). The risk was similar in patients with severe skin affection alone and those with psoriatic arthritis. CONCLUSIONS: Psoriasis is associated with increased risk of adverse cardiovascular events and all-cause mortality. Young age, severe skin affection and/or psoriatic arthritis carry the most risk. Patients with psoriasis may be candidates for early cardiovascular risk factor modification.

Metformin treatment is associated with a low risk of mortality in diabetic patients with heart failure: a retrospective nationwide cohort study.

AIMS/HYPOTHESIS: The safety of metformin in heart failure has been questioned because of a perceived risk of life-threatening lactic acidosis, though recent studies have not supported this concern. We investigated the risk of all-cause mortality associated with individual glucose-lowering treatment regimens used in current clinical practice in Denmark. METHODS: All patients aged ≥ 30 years hospitalised for the first time for heart failure in 1997-2006 were identified and followed until the end of 2006. Patients who received treatment with metformin, a sulfonylurea and/or insulin were included and assigned to mono-, bi- or triple therapy groups. Multivariable Cox proportional hazard regression models were used to assess the risk of all-cause mortality. RESULTS: A total of 10,920 patients were included. The median observational time was 844 days (interquartile range 365-1,395 days). In total, 6,187 (57%) patients died. With sulfonylurea monotherapy used as the reference, adjusted hazard ratios for all-cause mortality associated with the different treatment groups were as follows: metformin 0.85 (95% CI 0.75-0.98, p = 0.02), metformin + sulfonylurea 0.89 (95% CI 0.82-0.96, p = 0.003), metformin + insulin 0.96 (95% CI 0.82-1.13, p = 0.6), metformin + insulin + sulfonylurea 0.94 (95% CI 0.77-1.15, p = 0.5), sulfonylurea + insulin 0.97 (95% CI 0.86-1.08, p = 0.5) and insulin 1.14 (95% CI 1.06-1.20, p = 0.0001). CONCLUSIONS/INTERPRETATION: Treatment with metformin is associated with a low risk of mortality in diabetic patients with heart failure compared with treatment with a sulfonylurea or insulin.

Changes in short- and long-term cardiovascular risk of incident diabetes and incident myocardial infarction--a nationwide study.

AIMS/HYPOTHESIS: We assessed secular trends of cardiovascular outcomes following first diagnosis of myocardial infarction (MI) or diabetes in an unselected population. METHODS: All Danish residents aged > or = 30 years without prior diabetes or MI were identified by individual-level linkage of nationwide registers. Individuals hospitalised with MI or claiming a first-time prescription for a glucose-lowering medication (GLM) during the period from 1997 to 2006 were included. Analyses were by Poisson regression models. Primary endpoints were death by all causes, cardiovascular death and MI. RESULTS: The study included 3,092,580 individuals, of whom 77,147 had incident MI and 118,247 new-onset diabetes. MI patients had an increased short-term risk of all endpoints compared with the general population. The rate ratio (RR) for cardiovascular death within the first year after MI was 11.1 (95% CI 10.8-11.5) in men and 14.8 (14.3-15.3) in women, respectively. The risk rapidly declined and 1 year after the index MI, RR was 2.11 (2.00-2.23) and 2.8 (2.64-2.97) in men and women, respectively. Patients with diabetes carried a constantly elevated risk of all endpoints compared with the general population. The cardiovascular death RR was 1.90 (1.77-2.04) and 1.92 (1.78-2.07) in men and women, respectively during the first year after GLM initiation. CONCLUSIONS/INTERPRETATION: Incident MI is associated with high short-term risk, which decreases rapidly over time. Incident diabetes is associated with a persistent excessive cardiovascular risk after initiation of GLM therapy. This further strengthens the necessity of early multi-factorial intervention in diabetes patients for long-term benefit.

Potential of coded excitation in medical ultrasound imaging.

Improvement in signal-to-noise ratio (SNR) and/or penetration depth can be achieved in medical ultrasound by using long coded waveforms, in a similar manner as in radars or sonars. However, the time-bandwidth product (TB) improvement, and thereby SNR improvement is considerably lower in medical ultrasound, due to the lower available bandwidth. There is still space for about 20 dB improvement in the SNR, which will yield a penetration depth up to 20 cm at 5 MHz [M. O'Donnell, IEEE Trans. Ultrason. Ferroelectr. Freq. Contr., 39(3) (1992) 341]. The limited TB additionally yields unacceptably high range sidelobes. However, the frequency weighting from the ultrasonic transducer's bandwidth, although suboptimal, can be beneficial in sidelobe reduction. The purpose of this study is an experimental evaluation of the above considerations in a coded excitation ultrasound system. A coded excitation system based on a modified commercial scanner is presented. A predistorted FM signal is proposed in order to keep the resulting range sidelobes at acceptably low levels. The effect of the transducer is taken into account in the design of the compression filter. Intensity levels have been considered and simulations on the expected improvement in SNR are also presented. Images of a wire phantom and clinical images have been taken with the coded system. The images show a significant improvement in penetration depth and they preserve both axial resolution and contrast.

Arthritis associated with primary agammaglobulinemia: new clues to its immunopathology.

Primary agammaglobulinemia is a rare disorder which is associated with articular symptoms in 11% of patients. Septic arthritis may occur, but often patients complain of chronic oligoarthritis and have a clinical presentation similar to rheumatoid arthritis. We report 2 cases of primary agammaglobulinemia in adults, associated with non-erosive chronic arthritis. Peripheral blood lymphocyte phenotyping showed a predominance of CD8 lymphocytes with a CD4/CD8 ratio < 1. We did not find any abnormalities in cellular immunity. A histological study of the synovium showed chronic synovitis with perivascular CD8 lymphocyte infiltrates. Intravenous infusion of immunoglobulins resulted in a dramatic improvement in the arthritis in both cases. In one patient we noticed a decrease in CD8 lymphocytosis. These results suggest that CD8 lymphocytes are involved in the pathogenesis of the arthritis associated with agammaglobulinemia.