Governing biological material at the intersection of care and research: the use of dried blood spots for biobanking

A series of governance issues currently surrounds the multiple uses and multiple users of dried blood spots (DBS) for research purposes. Internationally there is a discussion on storing DBS resulting from newborn screening for public health and using them as the basis for large biobank-like collections to facilitate biomedical research. If such a transformation were to be formalized, then DBS would sit at the intersection of care (ie, public health) and research, with the mechanisms through which such a collection could be managed not totally self-evident. What is more, a DBS collection raises questions about the fuzzy boundaries between privacy and anonymity; how to control or define quality control uses of DBS; medical vs nonmedical uses; as well as benefit sharing and stakeholder involvement. Our goal here is to explore some of the key questions relating to DBS governance by way of the bio-objects and bio-objectification concepts. By embracing - rather than resisting to - the blurring of boundaries and problems in categorization that have come to characterize bio-objects and bio-objectification processes recently described in this journal, we attempt to highlight some issues that might not be currently considered, and to point to some possible directions to go (or avoid). Building from our knowledge of the current DBS situation in the Netherlands, we outline questions concerning the uses, management, collection, and storage of DBS.     

Manual derotation of the twisted spermatic cord

OBJECTIVE: To re-emphasize the safety and efficacy of manual derotation in the management of the twisted spermatic cord. PATIENTS AND METHODS: Seventeen patients (mean age 15 years, range 13-28) with acute unilateral torsion of the spermatic cord, initially treated by manual detorsion, were reviewed; all 17 patients were seen by one consulting urologist (H.F.M.K.). RESULTS: In 14 of the 17 patients the attempt resulted in successful manual derotation, i. e. the immediate relief of all symptoms and normal findings at physical examination. No testicular atrophy was detected during the follow-up (mean 22 months, range 9-72). CONCLUSIONS: These results reinforce the efficacy and safety of manual derotation with subsequent elective bilateral orchidopexy as the primary treatment for the twisted spermatic cord.     

Safety and utility of atropine addition during dobutamine stress echocardiography for the assessment of viable myocardium in patients with severe left ventricular dysfunction

Objective To assess the feasibility safety and side effects of the additionof atropine to dobutamine stress echocardio-graphy for the detectionof viable myocardium in patients with left ventricular dysfunction(ejection fraction 35%) prior to coronary revascularization. Background The assessment of viable and/or ischaemic myocardium has highprognostic value as regards improvement of function and survivalafter coronary revasculariz-ation. The addition of atropineto dobutamine during echocardiographic testing for the presenceof viable myocardium is not common practice. Consequently, nodata exist on the safety and additional diagnostic value ofthis practice. Methods Two hundred patients with left ventricular ejection fraction35% were studied. Results Test end-points were: target heart rate in 164 (82%) of thepatients, severe angina in 18 (9%), maximum dobutamine–atropinedose in six (3%), severe ST segment changes in five (2%), cardiacarrhythmias in four (2%), and hypotension in three (1%). Viabilitycould be assessed echocardiogaphically in 105/200 (53%) froma biphasic response (improvement of wall motion with low dosedobutamine and worsening with high dose), in 93 from ischaemiaand in 12 from sustained or late improvements. In 36/105 (34%)patients, ischaemic myocardium could only be assessed afterthe addition of atropine. Cardiac arrhythmias occurred in 11/200(6%) and hypotension (decrease of systolic blood pressure >30mmHg)in 21/200 (11%). Neither the use of atropine nor the inductionof ischaemia were associated with an increased incidence ofcardiac arrhythmias or hypotension. Conclusions In a large group of patients with severe left ventricular dysfunction,dobutamine stress echocardiography is feasible and safe in 186/200(93%); the addition of atropine was necessary in 34% to assessmyocardial viability. Hypotension and cardiac arrhythmias werethe most frequent side effects, but were not related to theinduction of ischaemia or addition of atropine.The EuropeanSociety of Cardiology     

Application of a vascular graft material (Solcograft-P) in experimental surgery

The implantation and post-implantation behaviour of a Solcograft-P vascular prosthesis in the aortic, aorto-iliac, carotid and vena caval positions in dogs was studied up to 100 d post-surgery in order to assess the suitability of this vascular material for use in man. Solcograft-P is prepared from the carotid arteries of calves by crosslinking the collagen stroma using adipyl dichloride. During the postoperative follow-up period of 3 month, 100% of the aortal grafts, 80% of the aorto-iliac bypasses, 60% of the vena caval grafts and 35% of the carotid implants remained patent. The biochemical properties of the Solcograft-P are better than those of Solcograft, its predecessor. The intimal lining was consistently smooth and homogeneous in grafts of biological origin, and no aneurysm was observed. Infection and early thrombosis occured no more frequently than with other grafts. The new Solcograft-P, crosslinked via ester and amide groups, seems to represent a real improvement over Solcograft. Our results suggest that Solcograft-P should prove valuable in various cases of reconstructive vascular surgery of the lower limb, especially when the autologous vena saphena magna is not available, and its mechanical properties may well prove suitable for both arterial and venous replacement.     

The association of ABCB1 polymorphisms and elevated serum digitoxin concentrations in geriatric patients

Objective Digitoxin is a known substrate of the efflux pump P-glycoprotein (gene name: ABCB1). P-glycoprotein expression was shown to be modulated by single nucleotide polymorphisms in the ABCB1 gene, but it remains unclear whether these polymorphisms influence digitoxin blood levels. Our objective was to examine the association of ABCB1 C3435T genotype and elevated serum digitoxin concentrations (SDC) in a cohort of 77 geriatric patients consecutively admitted to a geriatric department over a 12-month period. Methods The impact of ABCB1 3435 CC, CT, and TT genotypes on SDC and SDC normalized for daily digitoxin dosage and body weight was assessed by multivariate regression analysis. Results Among participants, 18 (23%) had the CC, 36 (47%) the CT, and 23 (30%) the TT genotype. Adjusting for relevant covariates, no significant association of ABCB1 C3435T genotype and SDC or normalized SDC was detected. Mean SDC was 22.4 ng/ml (95% CI 18.9–25.9) for the TT, 21.8 ng/ml (95% CI 18.1–25.5) for the CT, and 25.7 ng/ml (95% CI 20.6–30.8) for the CC genotype. The means for normalized SDC were 5.2 kg·l⁻¹ (95% CI 4.3–6.1) for the TT, 6.1 kg·l⁻¹ (95% CI 4.7–7.5) for the CT, and 6.2 kg·l⁻¹ (95% CI 4.6–7.7) for the CC genotype. Conclusion In this sample of frail geriatric patients, the impact of ABCB1 C3435T genotype on serum digitoxin concentration was not of major relevance. Regular monitoring of digitoxin blood levels and surveillance of appropriate drug use remain the best ways to prevent digitoxin intoxications in the elderly.     

Agreement and disagreement between “metabolic viability” and “contractile reserve” in akinetic myocardium

BACKGROUND: In patients with chronic coronary artery disease and depressed left ventricular function, assessment of residual viability in akinetic myocardium is important for therapeutic management. Intact perfusion, preserved metabolism, and presence of contractile reserve are different aspects of cellular viability. However, not all viable cells exhibit all characteristics; it is thought that contractile reserve is less often preserved compared with metabolic activity or intact perfusion. In this study we performed a direct comparison between perfusion imaging with thallium-201 single photon emission computed tomography (SPECT), metabolic imaging with F18-fluorodeoxyglucose SPECT, and assessment of contractile reserve with low-dose dobutamine echocardiography in akinetic myocardium. METHODS AND RESULTS: Forty patients with depressed left ventricular function (mean left ventricular ejection fraction 31% +/- 16%) were studied. Resting echocardiography showed akinesis in 165 (32%) segments. Most (n = 154, 93%) of these segments demonstrated resting hypoperfusion. F18-fluorodeoxyglucose imaging revealed a perfusion-metabolism mismatch in 41 segments and a match in 113 segments. Contractile reserve was present in 33 (80%) of the segments with a perfusion-metabolism mismatch and in 7 (6%) segments with a match (P < .0005). Of the 11 segments with normal perfusion, only 5 (45%) showed contractile reserve. The agreement between SPECT and dobutamine echocardiography was 87%. Although 94% of the segments that were nonviable on scintigraphy did not show contractile reserve, the disagreement between SPECT and dobutamine echocardiography was caused mainly by the absence of contractile reserve in 27% of the segments that were viable on scintigraphy. CONCLUSION: This study shows a good agreement between SPECT and dobutamine echocardiography, although a substantial number of segments with preserved viability on SPECT do not exhibit contractile reserve, indicating underestimation of viability by dobutamine echocardiography compared with F18-fluorodeoxyglucose imaging.