Differential regional decline in dopamine receptor availability across adulthood: Linear and nonlinear effects of age

Theories of adult brain development, based on neuropsychological test results and structural neuroimaging, suggest differential rates of age‐related change in function across cortical and subcortical sub‐regions. However, it remains unclear if these trends also extend to the aging dopamine system. Here we examined cross‐sectional adult age differences in estimates of D2‐like receptor binding potential across several cortical and subcortical brain regions using PET imaging and the radiotracer [¹⁸F]Fallypride in two samples of healthy human adults (combined N = 132). After accounting for regional differences in overall radioligand binding, estimated percent difference in receptor binding potential by decade (linear effects) were highest in most temporal and frontal cortical regions (~6–16% per decade), moderate in parahippocampal gyrus, pregenual frontal cortex, fusiform gyrus, caudate, putamen, thalamus, and amygdala (~3–5%), and weakest in subcallosal frontal cortex, ventral striatum, pallidum, and hippocampus (~0–2%). Some regions showed linear effects of age while many showed curvilinear effects such that binding potential declined from young adulthood to middle age and then was relatively stable until old age. Overall, these data indicate that the rate and pattern of decline in D2 receptor availability is regionally heterogeneous. However, the differences across regions were challenging to organize within existing theories of brain development and did not show the same pattern of regional change that has been observed in gray matter volume, white matter integrity, or cognitive performance. This variation suggests that existing theories of adult brain development may need to be modified to better account for the spatial dynamics of dopaminergic system aging.     

Unconventional treatment options in severe asthma: an overivew

In Canada, asthma is the leading cause of admission in hospital. About of 80% of the death from asthma is preventable. Severe asthma is defined as a patient with persistent symptoms despite the use of adequate controller therapy, including multiple courses of oral glucocorticosteroids. However, about 10% of patients with severe asthma remain poorly controlled despite optimal treatment and these patients have the greatest morbidity and mortality. The management of refractory severe asthma remains extremely challenging. For patients with refractory severe asthma, the adjunct therapies recommended by national guidelines only included oral glucocorticosteroid and anti-IgE antibody (omalizumab) therapy. Currently, there is limited published literature on the unconventional treatments of refractory severe asthma. The objective of this review article is to provide an updated therapeutic overview of unconventional treatment options for refractory severe asthma.     

Whole-genome sequencing for optimized patient management

Whole-genome sequencing of patient DNA can facilitate diagnosis of a disease, but its potential for guiding treatment has been under-realized. We interrogated the complete genome sequences of a 14-year-old fraternal twin pair diagnosed with dopa (3,4-dihydroxyphenylalanine)-responsive dystonia (DRD; Mendelian Inheritance in Man #128230). DRD is a genetically heterogeneous and clinically complex movement disorder that is usually treated with l-dopa, a precursor of the neurotransmitter dopamine. Whole-genome sequencing identified compound heterozygous mutations in the SPR gene encoding sepiapterin reductase. Disruption of SPR causes a decrease in tetrahydrobiopterin, a cofactor required for the hydroxylase enzymes that synthesize the neurotransmitters dopamine and serotonin. Supplementation of l-dopa therapy with 5-hydroxytryptophan, a serotonin precursor, resulted in clinical improvements in both twins.     

The Brief Negative Symptom Scale: Psychometric Properties

The participants in the NIMH-MATRICS Consensus Development Conference on Negative Symptoms recommended that an instrument be developed that measured blunted affect, alogia, asociality, anhedonia, and avolition. The Brief Negative Symptom Scale (BNSS) is a 13-item instrument designed for clinical trials and other studies that measures these 5 domains. The interrater, test–retest, and internal consistency of the instrument were strong, with respective intraclass correlation coefficients of 0.93 for the BNSS total score and values of 0.89–0.95 for individual subscales. Comparisons with positive symptoms and other negative symptom instruments supported the discriminant and concurrent validity of the instrument.     

Achievement of personalized pain goal in cancer patients referred to a supportive care clinic at a comprehensive cancer center

BACKGROUND:

Cancer pain initiatives recommend using the personalized pain goal to tailor pain management. This study was conducted to examine the feasibility and stability of personalized pain goal, and how it compares to the clinical pain response criteria.

METHODS:

Records of 465 consecutive cancer patients seen in consultation at the Supportive Care Clinic were reviewed. Pain relief was assessed as clinical response (≥30% or ≥2 point pain reduction) and personalized pain goal response (pain ≤ personalized pain goal).

RESULTS:

One hundred fifty‐two (34%), 95 (21%), and 163 (37%) patients presented with mild (1‐4), moderate (5‐6), and severe (7‐10) pain, respectively. Median age (59 years), males (52%), and advanced cancer status (84%) did not differ by pain category. Median personalized pain goal at initial clinic consult was 3 (interquartile range, 2‐3), was similar across pain groups, and remained unchanged (P = .57) at follow‐up (median, 14 days). Clinical response was higher among patients with severe pain (60%) as compared with moderate (40%) and mild pain (33%, P < .001). Personalized pain goal response was higher among patients with mild pain (63%) as compared with moderate (44%) and severe pain (27%, P < .001). By using personalized pain goal response as the gold standard for pain relief, the sensitivity of clinical response was highest (98%) among patients with severe pain, but it had low specificity (54%). In patients with mild pain, clinical response was most specific for pain relief (98%), but had low sensitivity (52%).

CONCLUSIONS:

Personalized pain goal is a simple patient‐reported outcome for pain goals. The majority of patients were capable of stating their desired level for pain relief. The median personalized pain goal was 3, and it was highly stable at follow‐up assessment. Cancer 2012. © 2011 American Cancer Society.     

Value of a new stick-type rapid urine test for the diagnosis of Helicobacter pylori infection in the Vietnamese population

AIM:To assess the value of a new test for the diagnosis of Helicobacter pylori(H.pylori) infection,Rapirun H.pylori Antibody Stick(Rapirun Stick),in a Vietnamese population.METHODS:Eligible patients without previous history of H.pylori eradication were recruited.Rapid urease test(RUT) and histologic examination were used to diagnose the H.pylori infection.Patients were considered H.pylori positive when the RUT results were positive and/or the bacteria were detected histologically.Rapirun Stick tests were performed using urine samples,and the results were compared with the other 2 methods.RESULTS:We enrolled 200 patients with a mean age of 36(range,18-76) years.There were 116 females and 84 males.Of the 200 patients,111(55.5%) were diagnosed as being H.pylori positive.The sensitivity,specificity,and accuracy of the Stick test were 84.7%,89.9%,and 87.0%,respectively.There were 17(8.5%) falsenegative patients and 9(4.5%) false-positive patients.CONCLUSION:The Rapirun Stick test has high sensitivity,specificity,and accuracy for the diagnosis of H.pylori infection in the Vietnamese population.The test can be clinically applied in Vietnamese populations.