Test–retest repeatability of [18F]Flortaucipir PET in Alzheimer’s disease and cognitively normal individuals

The aim of this study was to investigate the test–retest (TRT) repeatability of various parametric quantification methods for [¹⁸F]Flortaucipir positron emission tomography (PET). We included eight subjects with dementia or mild cognitive impairment due to Alzheimer’s disease and six cognitively normal subjects. All underwent two 130-min dynamic [¹⁸F]Flortaucipir PET scans within 3 ± 1 weeks. Data were analyzed using reference region models receptor parametric mapping (RPM), simplified reference tissue method 2 (SRTM2) and reference logan (RLogan), as well as standardized uptake value ratios (SUVr, time intervals 40–60, 80–100 and 110–130 min post-injection) with cerebellar gray matter as reference region. We obtained distribution volume ratio or SUVr, first for all brain regions and then in three tau-specific regions-of-interest (ROIs). TRT repeatability (%) was defined as |retest–test|/(average (test + retest)) × 100. For all methods and across ROIs, TRT repeatability ranged from (median (IQR)) 0.84% (0.68–2.15) to 6.84% (2.99–11.50). TRT repeatability was good for all reference methods used, although semi-quantitative models (i.e. SUVr) performed marginally worse than quantitative models, for instance TRT repeatability of RPM: 1.98% (0.78–3.58) vs. SUVr_80–100: 3.05% (1.28–5.52), p < 0.001. Furthermore, for SUVr_80–100 and SUVr_110–130, with higher average SUVr, more variation was observed. In conclusion, while TRT repeatability was good for all models used, quantitative methods performed slightly better than semi-quantitative methods.     

Urinary C-peptide creatinine ratio to detect absolute insulin deficiency in type 2 diabetes

BackgroundNational Institute for Health and Clinical Excellence guidelines (CG87) recommend neutral protamine hagedorn (NPH) insulin for the provision of basal insulin in type 2 diabetes, but use of analogue insulin is as much as 40%. Where residual endogenous insulin secretory capacity is present there is no evidence that analogue insulins provide any additional benefit over human insulins, and they come at an expensive premium. Anecdotally, however, there is a reluctance to switch people back to NPH insulin, partly because of a perceived risk of pancreatic failure and potential ketosis. Urinary C-peptide creatinine ratio (UCPCR) has been validated as a method for evaluating residual endogenous insulin secretion in type 1 and type 2 diabetes, with a UCPCR of no more than 0·2 nmol/mmol suggestive of absolute insulin deficiency. We aimed to evaluate the prevalence of true insulin deficiency among patients with type 2 diabetes with UCPCR, and confirm findings with the gold standard mixed meal tolerance test (MMTT).Methods191 insulin-treated patients with a clinical diagnosis of type 2 diabetes (diagnosed at or after age 45 years and who did not start insulin within the first year of diagnosis) collected a 2-h post-prandial urine sample for UCPCR measurement. Nine patients from two subgroups (UCPCR ≤0·2 nmol/mmol and UCPCR >0·2) completed a standard MMTT.Findings11 (5·8%) of 191 patients had two consistent UCPCRs of less than or equal to 0·2 nmol/mmol. Nine were able to do the MMTT, of whom five were confirmed to have absolute insulin deficiency (stimulated serum c-peptide <0·2 nmol/L). Three of these five patients were glutamic acid decarboxylase antibody-negative. Nine of nine patients with UCPCR of more than 0·2 nmol/L had confirmed endogenous insulin secretion in their MMTT. Those with insulin deficiency had a shorter time to starting insulin (median 2·5 years [IQR 1·5–3·0] vs 6·0 [3·0–10·75], p=0·005) and lower body-mass index (25 kg/m² vs 29, p=0·04) but no other significant differences in clinical characteristics.InterpretationWe have demonstrated a very low prevalence of true pancreatic failure in this population of insulin-treated patients with type 2 diabetes. This requires further exploration by comparison of a population being treated with NPH insulin with one on analogue insulin, and then determining whether UCPCR could act as a clinical decision support tool to safely switch from analogue insulin to NPH insulin.FundingNational Institute for Health Research.     

Currarino triad: Characteristic appearances on magnetic resonance imaging and plain radiography

The Currarino triad is a complex anomaly consisting of an anorectal malformation, a sacral bone defect and a presacral mass. It was first described in 1981 and since then, approximately 250 cases have been reported. Radiology has an important part to play in the diagnosis of this entity, as the imaging features are characteristic. We report a case of Currarino triad in an infant who presented with intractable constipation and discuss relevant MRI and plain radiography findings.     

Bronchial artery embolization: monitoring with somatosensory evoked potentials. Work in progress

Surgery remains the treatment of choice for massive and recurrent hemoptysis. In some instances, however, immediate surgical intervention is contraindicated. In these situations, bronchial artery embolization (BAE) has proved to be a successful definitive treatment for non-surgical candidates and a palliative therapy in patients requiring hemodynamic stabilization prior to surgery. The most serious complication of BAE is spinal cord ischemia. This relates directly to the potential anastomotic connections between the bronchial circulation and the anterior spinal artery. Somatosensory evoked potentials (SSEPs) have been used in the past to monitor spinal cord ischemia during procedures that threaten the vascularity of the spinal cord. The authors report two cases in which SSEPs were employed to monitor spinal cord ischemia during bronchial artery embolization.     

Analysis of antibody reactivities toward self antigens of IgM of patients with Waldenstrom's macroglobulinemia

By using a quantitative immunoblotting technique, we have analyzed the repertoires of antibody reactivities of IgM directed toward self antigens in the serum of patients with Waldenstrom's macroglobulinemia (WM) and in the serum of healthy adults. Monoclonal IgM of patients with WM expressed various degrees of polyreactivity and a high degree of heterogeneity with regard to the number and the nature of the protein bands that were recognized in homologous tissue extracts. Heterogeneous patterns of reactivity of WM IgM contrasted with the conserved profiles of reactivity of IgM in the serum of healthy blood donors. Protein bands that were recognized by WM IgM belonged to the restricted set of self antigens recognized in homologous tissues by normal polyclonal IgM, indicating the absence of a disease-specific reactivity profile of monoclonal WM IgM. Thus, monoclonal IgM that is present in large amounts in WM distorts the homogeneous pattern of reactivity of natural antibodies with self antigens which characterizes the natural antibody repertoire of healthy individuals.      

The transition from fetus to neonate – an endocrine perspective

Gluckman PD, Sizonenko SV, Bassett NS. The transition from fetus to neonate - an endocrine perspective. Acta Pædiatr 1999; Suppl 428: 7–11. Stockholm. ISSN 0803–5326
The transition from fetus to neonate involves three phases: late gestation, parturition and the processes needed to establish independent homoeostatic regulation after separation from the placenta. These phases are regulated by a series of fetal and placental endocrine events. Glucocorticoids have an important role in the preparation for birth, including involvement in lung and cardiac development, and the maturation of enzymes in a variety of pathways. Fetal Cortisol production is, in turn, also under hormonal control. Parturition is a complex process, which is still poorly understood in humans. The final steps are largely dependent on the effect of prostaglandin F_2α on the myometrium associated with increased oxytocin activity. The transition to birth is accompanied by changes in respiration, circulation, glucose homoeostasis, and the onset of independent oral feeding and thermoregulation. Several examples of endocrine components of the transition from fetal to neonatal life are reviewed here: the role of prostanoids, the onset of thermogenesis, and changes in the thyroid hormone and growth hormone axes. The effects of hormone levels on prematurity and growth retardation are also discussed. □ Birth transition, fetus, gestation, hormonal control, neonate, parturition