Effect of BH4 on blood phenylalanine and tyrosine variations in patients with phenylketonuria

BackgroundIn patients with phenylketonuria, stability of blood phenylalanine and tyrosine concentrations might influence brain chemistry and therefore patient outcome. This study prospectively investigated the effects of tetrahydrobiopterin (BH4), as a chaperone of phenylalanine hydroxylase on diurnal and day-to-day variations of blood phenylalanine and tyrosine concentrations.MethodsBlood phenylalanine and tyrosine were measured in dried blood spots (DBS) four times daily for 2 days (fasting, before lunch, before dinner, evening) and once daily (fasting) for 6 days in a randomized cross-over design with a period with BH4 and a period without BH4. The sequence was randomized. Eleven proven BH4 responsive PKU patients participated, 5 of them used protein substitutes during BH4 treatment. Natural protein intake and protein substitute dosing was adjusted during the period without BH4 in order to keep DBS phenylalanine levels within target range. Patients filled out a 3-day food diary during both study periods. Variations of DBS phenylalanine and Tyr were expressed in standard deviations (SD) and coefficient of variation (CV).ResultsBH4 treatment did not significantly influence day-to-day phenylalanine and tyrosine variations nor diurnal phenylalanine variations, but decreased diurnal tyrosine variations (median SD 17.6 μmol/l, median CV 21.3%, p = 0.01) compared to diet only (median SD 34.2 μmol/l, median CV 43.2%). Consequently, during BH4 treatment diurnal phenylalanine/tyrosine ratio variation was smaller, while fasting tyrosine levels tended to be higher.ConclusionBH4 did not impact phenylalanine variation but decreased diurnal tyrosine and phenylalanine/tyrosine ratio variations, possibly explained by less use of protein substitute and increased tyrosine synthesis.     

Analysis of exercise-induced R wave amplitude changes in detection of coronary artery disease in asymptomatic men with left bundle branch block

The exercise electrocardiograms of 44 asymptomatic men with acquired left bundle branch block were analyzed for changes in R wave amplitude. Results were correlated with findings on selective coronary angiography. There were two subgroups: 7 men with significant angiographic coronary artery disease (Group I) and 37 with normal coronary angiograms (Group II). Exercise induced an increase in R wave amplitude in all seven men with coronary artery disease but in only 10 of the 37 men without significant coronary artery disease. This criterion thus had a sensitivity of 100 percent but a poor specificity of 73 percent, a predictive value of 41 percent and an accuracy rate of 77 percent for the diagnosis of coronary artery disease. The greater the increase in R wave amplitude the greater was the likelihood of some degree of left ventricular dysfunction as measured by wall motion abnormalities and elevated left ventricular end-diastolic pressure. The increase in R wave amplitude with exercise appears to be a sensitive test in identifying coronary artery disease in asymptomatic men with acquired left bundle branch block.     

Plant neighbor detection through touching leaf tips precedes phytochrome signals

Plants in dense vegetation compete for resources, including light, and optimize their growth based on neighbor detection cues. The best studied of such behaviors is the shade-avoidance syndrome that positions leaves in optimally lit zones of a vegetation. Although proximate vegetation is known to be sensed through a reduced ratio between red and far-red light, we show here through computational modeling and manipulative experiments that leaves of the rosette species Arabidopsis thaliana first need to move upward to generate sufficient light reflection potential for subsequent occurrence and perception of a reduced red to far-red ratio. This early hyponastic leaf growth response is not induced by known neighbor detection cues under both climate chamber and natural sunlight conditions, and we identify a unique way for plants to detect future competitors through touching of leaf tips. This signal occurs before light signals and appears to be the earliest means of above-ground plant-plant signaling in horizontally growing rosette plants.     

Perceptions of sexuality and sexual health among young people in the Netherlands

Sexual health problems are not uncommon among young people in the Netherlands and finding the proper treatment for such problems is often challenging. More insight regarding young people's perceptions of sexuality and its associated problems is needed to improve both treatment and education. This qualitative study of 22 young people (aged 13 to 25 years) explored perceptions of sexuality and sexual health. The results show that sexuality is narrowly defined by young people, with focus clearly being placed on physical aspects of sexuality, and sexual intercourse in particular. Sexual problems are usually defined as physical or medical problems. The data show that participants had limited knowledge regarding sexual problems associated with sexual functioning. Schools, parents and culture all appear to play a role in perceptions of sexuality and sexual health. In their totality, the findings suggest that knowledge about the complexity of sexuality and sexual health is lacking among young people in the Netherlands. We recommend broader sexual health education programs in schools that include the discussion of multiple aspects of sexuality, including pleasure. We also suggest that parents take a more prominent role in educating their children about sexuality.     

Symptomatic Abdominal Aortic Aneurysm with Inferior Vena Cava Malposition

A 66-year old woman was admitted with an acute symptomatic abdominal aortic aneurysm. After preoperative assessment, she was directly operated on via transperitoneal approach.

Intraoperatively, a left-sided inferior vena cava was diagnosed. The preoperative study of the abdominal computed tomography had not revealed this venous malformation.

Retroperitoneal venous anomalies are a major source of unexpected haemorrhage during aortic reconstruction. Thus, for optimal preoperative preparation, a systematic close examination of the preoperative contrast enhanced CT scan of the abdomen is advised.     

Cost-effectiveness of nutritional intervention in elderly subjects after hip fracture. A randomized controlled trial

Summary

Hip fracture patients can benefit from nutritional supplementation during their recovery. Up to now, cost-effectiveness evaluation of nutritional intervention in these patients has not been performed. Costs of nutritional intervention are relatively low as compared with medical costs. Cost-effectiveness evaluation shows that nutritional intervention is likely to be cost-effective.

Introduction

Previous research on the effect of nutritional intervention on clinical outcome in hip fracture patients yielded contradictory results. Cost-effectiveness of nutritional intervention in these patients remains unknown. The aim of this study was to evaluate cost-effectiveness of nutritional intervention in elderly subjects after hip fracture from a societal perspective.

Methods

Open-label, multi-centre randomized controlled trial investigating cost-effectiveness of intensive nutritional intervention comprising regular dietetic counseling and oral nutritional supplementation for 3 months postoperatively. Patients allocated to the control group received care as usual. Costs, weight and quality of life were measured at baseline and at 3 and 6 months postoperatively. Incremental cost-effectiveness ratios (ICERs) were calculated for weight at 3 months and quality adjusted life years (QALYs) at 6 months postoperatively.

Results

Of 152 patients enrolled, 73 were randomized to the intervention group and 79 to the control group. Mean costs of the nutritional intervention was 613 Euro. Total costs and subcategories of costs were not significantly different between both groups. Based on bootstrapping of ICERs, the nutritional intervention was likely to be cost-effective for weight as outcome over the 3-month intervention period, regardless of nutritional status at baseline. With QALYs as outcome, the probability for the nutritional intervention being cost-effective was relatively low, except in subjects aged below 75 years.

Conclusion

Intensive nutritional intervention in elderly hip fracture patients is likely to be cost-effective for weight but not for QALYs. Future cost-effectiveness studies should incorporate outcome measures appropriate for elderly patients, such as functional limitations and other relevant outcome parameters for elderly.     

Advanced Imaging Modalities in Early Stage Breast Cancer: Preoperative Use in the United States Medicare Population

Background

Guidelines for breast cancer staging exist, but adherence remains unknown. This study evaluates patterns of imaging in early stage breast cancer usually reserved for advanced disease.

Methods

Surveillance Epidemiology, and End Results data linked to Medicare claims from 1992–2005 were reviewed for stage I/II breast cancer patients. Claims were searched for preoperative performance of computed tomography (CT), positron emission tomography (PET), bone scans, and brain magnetic resonance imaging (MRI) (“advanced imaging”).

Results

There were 67,874 stage I/II breast cancer patients; 18.8 % (n = 12,740) had preoperative advanced imaging. The proportion of patients having CT scans, PET scans, and brain MRI increased from 5.7 % to 12.4 % (P < 0.0001), 0.8 % to 3.4 % (P < 0.0001) and 0.2 % to 1.1 % (P = 0.008), respectively, from 1992 to 2005. Bone scans declined from 20.1 % to 10.7 % (P < 0.0001). “Breast cancer” (174.x) was the only diagnosis code associated with 62.1 % of PET scans, 37.7 % of bone scans, 24.2 % of CT, and 5.1 % of brain MRI. One or more symptoms or metastatic site was suggested for 19.6 % of bone scans, 13.0 % of CT, 13.0 % of PET, and 6.2 % of brain MRI. Factors associated (P < 0.05) with use of all modalities were urban setting, breast MRI and ultrasound. Breast MRI was the strongest predictor (P < 0.0001) of bone scan (odds ratio [OR] 1.63, 95 % confidence interval [CI] 1.44–1.86), Brain MRI (OR 1.74, 95 % CI 1.15–2.63), CT (OR 2.42, 95 % CI 2.12–2.76), and PET (OR 5.71, 95 % CI 4.52–7.22).

Conclusions

Aside from bone scans, performance of advanced imaging is increasing in early stage Medicare breast cancer patients, with limited rationale provided by coded diagnoses. In light of existing guidelines and increasing scrutiny about health care costs, greater reinforcement of current indications is warranted.